Lenalidomide in treatment-refractory cutaneous lupus erythematosus: Efficacy and safety in a 52-week trial

To the Editor: Patients with cutaneous lupus erythematosus (CLE) are frequently intolerant or refractory to traditional first-line treatment with antimalarials, and 10% remain recalcitrant to immunosuppressives or thalidomide. Thalidomide use is limited by side effects, including peripheral neuropathy and teratogenicity, and we thus studied lenalidomide (Revlimid), a thalidomide analog. (Source: Journal of the American Academy of Dermatology)

Correction: Lenalidomide Inhibits Lymphangiogenesis in Preclinical Models of Mantle Cell Lymphoma

(Source: Cancer Research)

POEMS syndrome: 2014 Update on diagnosis, risk‚?źstratification, and management

Disease overview: POEMS syndrome is a paraneoplastic syndrome due to an underlying plasma cell neoplasm. The major criteria for the syndrome are polyradiculoneuropathy, clonal plasma cell disorder (PCD), sclerotic bone lesions, elevated vascular endothelial growth factor, and the presence of Castleman disease. Minor features include organomegaly, endocrinopathy, characteristic skin changes, papilledema, extravascular volume overload, and thrombocytosis. Diagnoses are often delayed because the syndrome is rare and can be mistaken for other neurologic disorders, most commonly chronic inflammatory demyelinating polyradiculoneuropathy. POEMS syndrome should be distinguished from the Castleman disease variant of POEMS syndrome, which has no clonal PCD and typically little to no peripheral neuro...

Bendamustine-bortezomib-dexamethasone is an active and well-tolerated regimen in patients with relapsed or refractory multiple myeloma

Bendamustine with bortezomib and dexamethasone was evaluated in 79 patients with relapsed/refractory multiple myeloma. Median age was 64 years, and patients had a median of 2 prior treatment lines (range, 1 to 6 lines). Bendamustine 70 mg/m2 days 1 and 4; bortezomib 1.3 mg/m2 intravenously days 1, 4, 8, and 11; and dexamethasone 20 mg days 1, 4, 8, and 11 once every 28 days was given for up to 8 cycles. Primary end point was overall response rate (ORR). Secondary end points were progression-free survival (PFS), overall survival, time to response, and toxicity. ORR was 60.8%, and when minor responses were included, 75.9%. Median time to response was 31 days. ORR rate was similar in patients previously exposed to bortezomib, lenalidomide, and bortezomib plus lenalidomide. PFS was 9.7 and OS ...

Low-dose lenalidomide plus cytarabine induce complete remission that can be predicted by genetic profiling in elderly acute myeloid leukemia patients

Authors: G Visani, F Ferrara, F Di Raimondo, F Loscocco, G Sparaventi, S Paolini, F Fuligni, A Gazzola, M Rossi, M A Laginestra, M R Caraci, C Riccardi, M Rocchi, A Visani, S A Pileri, P P Piccaluga & A Isidori (Source: Leukemia)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Outcomes and treatments of patients with immunoglobulin light chain amyloidosis who progress or relapse post autologous stem cell transplant

In conclusion our study indicates that patients with AL amyloidosis fare well post‚?źtransplant relapse/progression. Additionally, it provides a yardstick to design clinical trials to determine best treatment options. This article is protected by copyright. All rights reserved. (Source: European Journal of Haematology)

European Myeloma Network recommendations on the evaluation and treatment of newly diagnosed patients with multiple myeloma.

This article presents recommendations of the European Myeloma Network for newly diagnosed patients based on the GRADE system for level of evidence. All patients with symptomatic disease should undergo risk stratification to classify patients for International Staging System stage (level of evidence: 1A) and for cytogenetically defined high- versus standard-risk groups (2B). Novel-agent-based induction and up-front autologous stem cell transplantation in medically fit patients remains the standard of care (1A). Induction therapy should include a triple combination of bortezomib, with either adriamycin or thalidomide and dexamethasone (1A), or with cyclophosphamide and dexamethasone (2B). Currently, allogeneic stem cell transplantation may be considered for young patients with high-risk dise...

Update on treatment of light chain amyloidosis.

Authors: Mahmood S, Palladini G, Sanchorawala V, Wechalekar A Abstract Light chain amyloidosis is the most common type of amyloidosis as a consequence of protein misfolding of aggregates composed of amyloid fibrils. The clinical features are dependent on the organs involved, typically cardiac, renal, hepatic, peripheral and autonomic neuropathy and soft tissue. A tissue biopsy or fat aspirate is needed to confirm the presence/type of amyloid and prognostic tools are important in a risk stratified approach to treatment. Autologous stem cell transplant eligibility should be assessed at baseline, weighing the reversible or non-reversible contraindications, toxicity of treatment and chemotherapy alternatives available. Chemotherapy options include melphalan, thalidomide, bortezomib, le...

A novel small molecule inhibitor of deubiquitylating enzyme USP14 and UCHL5 induces apoptosis in multiple myeloma and overcomes bortezomib resistance

Proteasome inhibitors have demonstrated that targeting protein degradation is effective therapy in multiple myeloma (MM). Here we show that deubiquitylating enzymes (DUBs) USP14 and UCHL5 are more highly expressed in MM cells than in normal plasma cells. USP14 and UCHL5 short interfering RNA knockdown decreases MM cell viability. A novel 19S regulatory particle inhibitor b-AP15 selectively blocks deubiquitylating activity of USP14 and UCHL5 without inhibiting proteasome activity. b-AP15 decreases viability in MM cell lines and patient MM cells, inhibits proliferation of MM cells even in the presence of bone marrow stroma cells, and overcomes bortezomib resistance. Anti-MM activity of b-AP15 is associated with growth arrest via downregulation of CDC25C, CDC2, and cyclin B1 as well as induct...

Anti‚?źő≤2M monoclonal antibodies kill myeloma cells via cell‚?ź and complement‚?źmediated cytotoxicity

In this study, we investigated the ability of the mAbs at much lower concentrations to indirectly kill myeloma cells by utilizing immune effector cells or molecules. Our results showed that anti‚?źő≤2M mAbs effectively lysed MM cells via antibody‚?źdependent cell‚?źmediated cytotoxicity (ADCC) and complement‚?źdependent cytotoxicity (CDC), which were correlated with and dependent on the surface expression of ő≤2M on MM cells. The presence of MM bone marrow stromal cells or addition of IL‚?ź6 did not attenuate anti‚?źő≤2M mAb‚?źinduced ADCC and CDC activities against MM cells. Furthermore, anti‚?źő≤2M mAbs only showed limited cytotoxicity toward normal B cells and non‚?źtumorous mesenchymal stem cells, indicating that the ADCC and CDC activities of the anti‚?źő≤2M mAbs were more prone to th...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Myelodysplastic syndromes: 2014 update on diagnosis, risk‚?źstratification, and management

Disease overview: The myelodysplastic (MDS) are a very heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increased risk of transformation to acute myelogenous leukemia (AML). MDS occurs more frequently in older male and in individuals with prior exposure to cytotoxic therapy. Diagnosis: Diagnosis of MDS is based on morphological evidence of dysplasia upon visual examination of a bone marrow aspirate and biopsy. Information obtained from additional studies such as karyotype, flow cytometry or molecular genetics is complementary but not diagnostic. Risk‚?źstratification: Prognosis of patients with MDS can be calculated using a number of scoring systems. In general, all these scoring systems include analysis of peripheral cytopenias, percentage of blast...

[Report] The Myeloma Drug Lenalidomide Promotes the Cereblon-Dependent Destruction of Ikaros Proteins

A drug with potent activity in multiple myeloma patients acts by inducing degradation of two specific transcription factors. [Also see Perspective by Stewart] Authors: Gang Lu, Richard E. Middleton, Huahang Sun, MarkVic Naniong, Christopher J. Ott, Constantine S. Mitsiades, Kwok-Kin Wong, James E. Bradner, William G. Kaelin (Source: Science: Current Issue)

[Report] Lenalidomide Causes Selective Degradation of IKZF1 and IKZF3 in Multiple Myeloma Cells

A drug with potent activity in multiple myeloma patients acts by inducing degradation of two specific transcription factors. [Also see Perspective by Stewart] Authors: Jan Krönke, Namrata D. Udeshi, Anupama Narla, Peter Grauman, Slater N. Hurst, Marie McConkey, Tanya Svinkina, Dirk Heckl, Eamon Comer, Xiaoyu Li, Christie Ciarlo, Emily Hartman, Nikhil Munshi, Monica Schenone, Stuart L. Schreiber, Steven A. Carr, Benjamin L. Ebert (Source: Science: Current Issue)

A prospective study of lenalidomide monotherapy for relapse after Allo-SCT for multiple myeloma

Authors: W I Bensinger, D J Green, N Burwick & P S Becker (Source: Bone Marrow Transplantation)

Mechanism of immunomodulatory drugs' action in the treatment of multiple myeloma.

Authors: Chang X, Zhu Y, Shi C, Stewart AK Abstract Although immunomodulatory drugs (IMiDs), such as thalidomide, lenalidomide, and pomalidomide, are widely used in the treatment of multiple myeloma (MM), the molecular mechanism of IMiDs' action is largely unknown. In this review, we will summarize recent advances in the application of IMiDs in MM cancer treatment as well as their effects on immunomodulatory activities, anti-angiogenic activities, intervention of cell surface adhesion molecules between myeloma cells and bone marrow stromal cells, anti-inflammatory activities, anti-proliferation, pro-apoptotic effects, cell cycle arrest, and inhibition of cell migration and metastasis. In addition, the potential IMiDs' target protein, IMiDs' target protein's functional role, and the...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

From ASH‚??multiple myeloma: Options for patients ineligible for stem-cell transplantation

Nature Reviews Clinical Oncology 11, 67 (2014). doi:10.1038/nrclinonc.2013.240 The standard treatment for patients with newly diagnosed multiple myeloma (NDMM) is a combination of melphalan, prednisone, and thalidomide (MPT). The phase IIITMM-020/IFM 07 01 trial compared the efficacy and safety of combining lenalidomide and low-dose dexamethasone (Rd) with MPT. The study included 1,623 patients (Source: Nature Clinical Practice Oncology)

Multiple myeloma: Destruction of Ikaros

Nature Reviews Cancer 14, 9 (2014). doi:10.1038/nrc3663 Author: Sarah Seton-Rogers The thalidomide-like drug lenalidomide is used to treat multiple myeloma, but its mechanism of action is not known. Two studies have shown that lenalidomide induces proteasomal degradation of Ikaros family zinc finger protein 1 (IKZF1) and IKZF3 through cereblon (CRBN), a substrate-recognition component of a (Source: Nature Reviews Cancer)

Inside This Issue

See ‚??Endothelium-mediated survival of leukemic cells and angiogenesis-related factors are affected by lenalidomide treatment in chronic lymphocytic leukemia,‚?Ě Maffei et¬†al., pages 126‚??136. (Source: Experimental Hematology)

Characterization of the RhoH C Terminus and Insert Domain [Cell Biology]

RhoH is a hematopoietic-specific, GTPase-deficient member of the Rho GTPase family that was first identified as a hypermutable gene in human B lineage lymphomas. RhoH remains in a constitutively active state and thus its effects are regulated by expression levels or post-translational modifications. Similar to other small GTPases, intracellular localization of RhoH is dependent upon the conserved ‚??CAAX‚?Ě box and surrounding sequences within the carboxyl (C) terminus. However, RhoH also contains a unique C-terminal ‚??insert‚?Ě domain of yet undetermined function. RhoH serves as adaptor molecule in T cell receptor signaling and RhoH expression correlates with the unfavorable prognostic marker ZAP70 in human chronic lymphocytic leukemia. Disease progression is attenuated in a Rhoh‚??/‚?? ...

Smoldering multiple myeloma requiring treatment: time for a new definition?

Smoldering multiple myeloma (SMM) bridges the gap between monoclonal gammopathy of undetermined significance (a mostly premalignant disorder) and active multiple myeloma (MM). Until recently, no interventional study in patients with SMM showed improved overall survival (OS) with therapy as compared with observation. A report from the PETHEMA-GEM (Programa Espa&ntilde;ol de Tratamientos en Hematologica) group described both fewer myeloma-related events and better OS among patients with high-risk SMM who were treated with lenalidomide and dexamethasone. This unique study prompted us to review current knowledge about SMM and address the following questions: (1) Are there patients currently defined as SMM who should be treated routinely? (2) Should the definitions of SMM and MM be reconsidered...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Increase in antibody dependent cellular cytotoxicity (ADCC) in a patient with advanced colorectal carcinoma carrying a KRAS mutation under lenalidomide therapy.

Authors: Gamerith G, Auer T, Amann A, Putzer D, Schenk B, Kircher B, Hilbe W, Zwierzina H, Loeffler-Ragg J Abstract The failure of EGFR inhibitors in colorectal tumors with KRAS mutations requires the development of alternative treatment strategies for this patient subgroup. Among the hallmarks of cancer the disturbed immunosurveillance and cancer immune evasion have become emerging targets for cancer therapy. Due to their pleiotropic functions immunomodulatory drugs (IMiDs) are interesting agents for combination therapies in solid tumors. However, their possible contribution and a way of monitoring their biological effects have yet to be revealed. In a heavily pretreated patient with advanced colorectal cancer carrying mutations in APC and KRAS genes, we show an early metabolic re...

Haematological cancer: Ikaros‚??not a myth for myeloma

Nature Reviews Clinical Oncology 11, 65 (2014). doi:10.1038/nrclinonc.2013.237 Author: Alessia Errico Lenalidomide is a powerful drug for the treatment of multiple myeloma and other B-cell lymphomas. Two independent groups, respectively, led by Benjamin Ebert and William Kaelin, recently reported that degradation of the ikaros proteins, IKZF1 and IKZF3, is the main event underlying lenalidomide antineoplastic function, (Source: Nature Clinical Practice Oncology)

Anti-Lymphangiogenesis by Lenalidomide in MCL

Lymphomas originate in and spread primarily along the lymphatic system. However, whether lymphatic vessels contribute to the growth and spreading of lymphomas is largely unclear. Mantle cell lymphoma (MCL) represents an aggressive non-Hodgkin's lymphoma. We found that MCL exhibited abundant intratumor lymphatic vessels. Our results demonstrated that the immunomodulatory drug lenalidomide potently inhibited the growth and dissemination of MCL in a xenograft MCL mouse model, at least in part, by inhibiting functional tumor lymphangiogenesis. Significant numbers of tumor-associated macrophages expressing vascular endothelial growth factor-C were found in both human MCL and mouse MCL xenograft samples. Lenalidomide treatment resulted in a significant reduction in the number of MCL-associated m...

Immunomodulatory agents lenalidomide and pomalidomide co‚?źstimulate T cells by inducing degradation of T cell repressors Ikaros and Aiolos via modulation of the E3 ubiquitin ligase complex CRL4CRBN

In conclusion, we present a molecular model in which drug binding to cereblon results in the interaction of Ikaros and Aiolos to CRL4CRBN, leading to their ubiquitination, subsequent proteasomal degradation and T cell activation. (Source: British Journal of Haematology)

Reactive angioendotheliomatosis associated with cyroglobulinemia in a marathon runner.

We report a case of a 65-year-old marathon runner who presented with painful plaques, which were worse in cold weather and progressed to ulceration. A punch biopsy revealed vascular endothelial hyperplasia and an appearance consistent with reactive angioendotheliomatosis (RAE), a rare, but benign disorder of the skin. Subsequent investigations resulted in the diagnosis of type I cryoglobulinemia; the lesions resolved completely following treatment of the underlying disorder with lenalidomide. PMID: 24314779 [PubMed - in process] (Source: Dermatol Online J)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Revlimid Slows Multiple Myeloma Relapse (CME/CE)

NEW ORLEANS (MedPage Today) -- For patients whose multiple myeloma is in remission after initial therapy, maintenance with the immune modulator lenalidomide (Revlimid) prolongs the time to relapse, a researcher said here. (Source: MedPage Today Hematology/Oncology)

Improved survival in myeloma patients: starting to close in on the gap between elderly patients and a matched normal population

Summary The outcome for multiple myeloma patients has improved since the introduction of bortezomib, thalidomide and lenalidomide. However, studies comparing new and conventional treatment include selected patient groups. We investigated consecutive patients (n¬†=¬†1638) diagnosed in a defined period and compared survival with a gender‚?ź and age‚?źmatched cohort Swedish population (n¬†=¬†9¬†340¬†682). Median overall survival for non‚?źhigh‚?źdose treated patients was 2¬∑8¬†years. The use of bortezomib, thalidomide or lenalidomide in first line therapy predicted a significantly longer overall survival (median 4¬∑9¬†years) compared to conventional treatment (2¬∑3¬†years). Among non‚?źhigh‚?źdose treated patients receiving at least 2 lines with bortezomib, thalidomide or lenalidomide, 69% an...

Screening thalidomide analogs [Biological Sciences]

We thank D‚??Amato et al. (1) and Zeldis et al. (2) for their interest and comments on our article in PNAS (3). We carried out a screen of lenalidomide and pomalidomide primarily in chicken and zebrafish embryos, but also in several in vitro assays. Our goal was to determine any... (Source: Proceedings of the National Academy of Sciences)

Lenalidomide Plus Dex Trumps Standard Tx in Multiple MyelomaLenalidomide Plus Dex Trumps Standard Tx in Multiple Myeloma

Combining lenalidomide with low-dose dexamethasone improved progression-free survival as first-line tx in multiple myeloma, compared with the standard melphalan, prednisone plus thalidomide. Medscape Medical News (Source: Medscape Today Headlines)

Bortezomib, lenalidomide and dexamethasone (VRD) combination as salvage therapy in refractory angioimmunoblastic T cell lymphoma

(Source: British Journal of Haematology)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Natural killer T cell defects in multiple myeloma and the impact of lenalidomide therapy

Summary The causes of multiple myeloma (MM) remain obscure and there are few known risk factors; however, natural killer T (NKT) cell abnormalities have been reported in patients with MM, and therapeutic targeting of NKT cells is promoted as a potential treatment. We characterized NKT cell defects in treated and untreated patients with MM and determined the impact of lenalidomide therapy on the NKT cell pool. Lenalidomide is an immunomodulatory drug with co‚?źstimulatory effects on NKT cells in vitro and is an approved treatment for MM, although its mode of action in that context is not well defined. We find that patients with relapsed/progressive MM had a marked deficiency in NKT cell numbers. In contrast, newly diagnosed patients had relatively normal NKT cell frequency and function prio...

Consolidation and maintenance therapy with lenalidomide, bortezomib and dexamethasone (RVD) in high-risk myeloma patients

Authors: A K Nooka, J L Kaufman, S Muppidi, A Langston, L T Heffner, C Gleason, D Casbourne, D Saxe, L H Boise & S Lonial (Source: Leukemia)

Haematological and molecular responses in refractory anaemia with ring sideroblasts and thrombocytosis treated with lenalidomide

(Source: European Journal of Haematology)

HIF-1őĪ of bone marrow endothelial cells implies relapse and drug resistance in patients with multiple myeloma and may act as a therapeutic target.

CONCLUSIONS: The HIF-1őĪ protein in MMECs may induce angiogenesis and resistance to bortezomib and lenalidomide and be a plausible target for the antiangiogenic management of well defined relapsed/refractory MM patients. It may also have prognostic significance. PMID: 24297864 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Case of angioedema and urticaria induced by lenalidomide

(Source: The Journal of Dermatology)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Deletion 5q MDS: Molecular and therapeutic implications

Heterozygous, interstitial deletions of chromosome 5q are the most common cytogenetic abnormality in myelodysplastic syndromes (MDS). This chromosomal abnormality is associated with a consistent clinical phenotype, the 5q- syndrome, in a subset of patients, and therapeutic sensitivity to the drug lenalidomide. No genes on chromosome 5q undergo recurrent homozygous inactivation in MDS patients. Instead, haploinsufficiency for key genes powerfully alters hematopoiesis, leading to the MDS phenotype in patients with del(5q). Haploinsufficiency for the RPS14 gene leads to activation of the p53 pathway and the macrocytic anemia characteristic of this disorder, and loss of p53 rescues erythropoiesis and facilitates clonal progression. Other genes, as well as miR-145 and miR-146a, contribute to ab...

Lenalidomide for myelodysplastic syndromes with del(5q): how long should it last?

In conclusion, long‚?źlasting remissions are achievable in MDS patients with del(5q) in complete response after lenalidomide discontinuation. Copyright ¬© 2014 John Wiley & Sons, Ltd. (Source: Hematological Oncology)

Mature results of MM‚?ź011: A phase I/II trial of liposomal doxorubicin, Vincristine, Dexamethasone, and Lenalidomide combination therapy followed by lenalidomide maintenance for relapsed/refractory multiple myeloma

We report the long‚?źterm outcomes of all 76 treated patients with follow‚?źup ‚?•5 years. This single‚?źcenter phase I/II study administered lenalidomide (10 mg on days 1‚??21 of every 28‚?źday cycle), intravenous liposomal doxorubicin (40 mg/m2 on day 8), dexamethasone (40 mg on days 8‚??11), and intravenous vincristine (2 mg on day 8). After 4‚??6 planned induction cycles, lenalidomide maintenance therapy was given at the last tolerated dose until progression, with or without 50 mg prednisone every other day. The median number of previous therapies was 3 (range, 1‚??7); 49 (64.5%) patients had refractory disease. Forty‚?źthree (56.6%) patients received maintenance therapy. Grade 3/4 adverse events occurred during induction and maintenance therapy in 48.7% and 25.6% of patients, respecti...

Long‚?źterm disease control in patients with newly diagnosed multiple myeloma after suspension of lenalidomide therapy

Abstract There are no systematic data regarding non‚?źmaintained induction for those patients with multiple myeloma (MM) who do not receive consolidative autologous stem cell transplantation. Of 173 patients with newly diagnosed MM treated with lenalidomide and dexamethasone (LenDex) as primary therapy, thirty‚?źone patients had their lenalidomide discontinued for reasons other than progression or alternate therapy. Median progression free survival (PFS) from the time of discontinuing lenalidomide was longer in patients who received lenalidomide ‚?•1 year (39 versus 13 months, p&lt;0.05); there was no difference in PFS for those treated for 1‚?ź2 years as compared to ‚?•2 years. Among those taking lenalidomide for ‚?•1 year PFS was superior in patients who were in very good partial respons...

IMiDs: Not for the CRBN weak

Cereblon (CRBN) is believed to be the cellular target responsible for the anti-MM activity of IMiDs . Supporting this concept are recent publications demonstrating significant correlation between CRBN expression and therapeutic response to either upfront Rd or maintenance thalidomide . The accompanying manuscript by Schuster et al. confirms low CRBN expression as a definitive predictor of IMiD resistance. Within a dataset of relapsed refractory MM, no patient with low (bottom quartile) CRBN expression responded to single agent IMiD (with or without dex), regardless of the IMiD employed (thalidomide, lenalidomide or pomalidomide). For these patients, low CRBN expression predicted significantly reduced PFS and OS. In contrast, CRBN expression failed to predict response to aggressive multi-ag...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Management of Relapses After Hematopoietic Cell Transplantation in T-Cell Non-Hodgkin Lymphomas

T-cell non-Hodgkin lymphomas (NHLs) are a heterogeneous group of malignancies that represent 10%‚??15% of all NHLs. The prognosis of relapsed T-cell NHL is poor, especially for those relapsing after an autologous (auto-) or allogeneic (allo-) hematopoietic cell transplantation (HCT). Disease relapse post auto-HCT is best managed on a clinical trial. In the absence of an investigational protocol, the choice of salvage therapies should take into account patient performance status, eligibility for an allo-HCT, and surface CD30 expression. CD30-directed therapies or aggressive salvage regimens can be used as a bridge to allo-HCT in medically fit patients. In the elderly or more infirm patients, single-agent therapies could be offered, aiming at palliation. Similarly, relapse after an allo-HCT ...

AT‚?ź101 downregulates BCL2 and MCL1 and potentiates the cytotoxic effects of lenalidomide and dexamethasone in preclinical models of multiple myeloma and Waldenstr√∂m macroglobulinaemia

Summary Multiple myeloma, the second most common haematological malignancy in the U.S., is currently incurable. Disruption of the intrinsic apoptotic pathway by BCL2 and MCL1 upregulation is observed in &gt;80% of myeloma cases and is associated with an aggressive clinical course. Remarkably, there is no approved drug with the ability to target BCL2 or MCL1. Thus, we investigated the anti‚?źtumour effects of a pan‚?źBCL2 inhibitor, AT‚?ź101, which has high binding specificity for BCL2 and MCL1 in preclinical models of plasma cell cancers (Multiple myeloma and Waldenstr√∂m macroglobulinaemia). Gene expression and immunoblot analysis of six plasma cell cancer models showed upregulation of BCL2 family members. AT‚?ź101 was able to downregulate BCL2 and MCL1 in all plasma cell cancer models an...

ASH 2013 Preview: More Than 100 Interesting and Important Myeloma Abstracts

The IMF team reviewed the more than 800 ASH 2013 abstracts that were released last week and identified 131 myeloma abstracts worthy of specific comment. One of the top plenary session abstracts for ASH this year is the MM-020 study of Revlimid in newly diagnosed myeloma patients, says IMF Chairman Dr. Brian Durie. In the first of his two-part overview of the ASH 2013 abstracts, he focuses on those that looked at novel agents (Source: International Myeloma Foundation)

Polyarteritis nodosa complicating multiple myeloma - a case report and review of the literature.

Conclusion: This is a remarkable case of a histologically confirmed peripheral neuropathy due to polyarteritis nodosa associated with progression of MGUS to multiple myeloma. Immediate diagnosis and combined immunosuppressive and anti-neoplastic treatment may improve the outcome of this potentially life-threatening clinical condition. PMID: 24220008 [PubMed - as supplied by publisher] (Source: Clinical Neuropathology)

Long-term response to lenalidomide in patients with newly diagnosed multiple myeloma

Authors: T V Kourelis, S K Kumar, G Srivastava, M A Gertz, M Q Lacy, F K Buadi, R A Kyle & A Dispenzieri (Source: Leukemia)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Extended survival and reduced risk of AML progression in erythroid-responsive lenalidomide-treated patients with lower-risk del(5q) MDS

Authors: A F List, J M Bennett, M A Sekeres, B Skikne, T Fu, J M Shammo, S D Nimer, R D Knight & A Giagounidis (Source: Leukemia)

[Therapy of multiple myeloma : What is confirmed?]

Authors: Peest D, Ganser A, Einsele H Abstract Multiple myeloma (MM) is a malignant plasma cell disorder with clonal development. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) are precursor stages of MM and both have to be differentiated from MM which is characterized by organ complications. High-dose chemotherapy combined with autologous stem cell support is the therapy of choice for most patients in order to achieve long-lasting complete remission with few symptoms, prevention of new organ complications and survival prolongation. Patients who cannot be intensively treated due to advanced age and comorbidities should be treated with low-dose chemotherapy, normally alkylating agents, for improved quality of life and also survival pr...

Hematological and molecular responses in refractory anemia with ring sideroblasts and thrombocytosis (RARS‚?źT) treated by Lenalidomide

This article is protected by copyright. All rights reserved. (Source: European Journal of Haematology)

Global real-time quantitative reverse transcription-polymerase chain reaction detecting proto-oncogenes associated with 14q32 chromosomal translocation as a valuable marker for predicting survival in multiple myeloma

Abstract: CCND1, FGFR3 and c-MAF mRNA expression of tumor samples from 123 multiple myeloma patients were analyzed by global RQ/RT-PCR. CCND1, FGFR3 and c-MAF were positive in 44 (36%), 28 (23%) and 16 (13%) of patients, respectively. In 7 patients, both FGFR3 and c-MAF were positive. The expression of c-MAF was independent unfavorable prognostic factors for overall survival (OS). Autologous stem cell transplantation improved progression-free survival of CCND1-positive patients. Bortezomib, thalidomide or lenalidomide extended OS of FGFR3 and/or c-MAF-positive patients. Thus, CCND1, FGFR3 and c-MAF mRNA expression can predict survival and is useful for planning stratified treatment strategies for myeloma patients. (Source: Leukemia Research)

Prediction of Poor Mobilization of Autologous CD34+ Cells with Growth Factor in Multiple Myeloma Patients: Implications for Risk-Stratification

Abstract: It is unknown whether clinical characteristics can successfully predict which multiple myeloma (MM) patients would be poor mobilizers with growth factor (GF) alone so they can be assigned to mobilization with chemotherapy + GF or GF + plerixafor. MM patients (N = 477) who underwent autologous mobilization with GF were retrospectively reviewed and assigned into training and validation cohorts. In multiple regression analysis, age, platelet count at time of mobilization, type of GF utilized, and extent of exposure to lenalidomide independently correlated with peripheral blood (PB)-CD34+ and were integrated in a predicting score (PS) for poor mobilizers, defined as PB-CD34+  (Source: Biology of Blood and Marrow Transplantation)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Endothelium-mediated survival of leukemic cells and angiogenesis-related factors are affected by lenalidomide treatment in chronic lymphocytic leukemia

In conclusion, our study provides further evidence that the anti-CLL effect of lenalidomide is mediated through the alteration of microenvironmental elements, implying the modulation of several angiogenesis-related factors and disruption of CLL crosstalk with endothelial cells. (Source: Experimental Hematology)

Phase 2 trial of intravenously administered plerixafor for stem cell mobilization in patients with multiple myeloma following lenalidomide-based initial therapy

Authors: S K Kumar, J Mikhael, B LaPlant, M Q Lacy, F K Buadi, D Dingli, M A Gertz, K Laumann, T Miceli, M Mahlman, L P Bergsagel, S R Hayman, C Reeder, A K Stewart, A Dispenzieri, D A Gastineau & J L Winters (Source: Bone Marrow Transplantation)

Phase 2 dose-expansion study (PX-171-006) of carfilzomib, lenalidomide, and low-dose dexamethasone in relapsed or progressive multiple myeloma

We previously reported a phase 1b dose-escalation study of carfilzomib, lenalidomide, and low-dose dexamethasone (CRd) in relapsed or progressive multiple myeloma where the maximum planned dose (MPD) was carfilzomib 20 mg/m2 days 1 and 2 of cycle 1 and 27 mg/m2 days 8, 9, 15, 16, and thereafter; lenalidomide 25 mg days 1 to 21; and dexamethasone 40 mg once weekly on 28-day cycles. Herein, we present results from the phase 2 dose expansion at the MPD, focusing on the 52 patients enrolled in the MPD cohort. Median follow-up was 24.4 months. In the MPD cohort, overall response rate (ORR) was 76.9% with median time to response of 0.95 month (range, 0.5-4.6) and duration of response (DOR) of 22.1 months. Median progression-free survival was 15.4 months. ORR was 69.2% in bortezomib-refractory pa...

Antitumoral activity of lenalidomide in in vitro and in vivo models of mantle cell lymphoma involves the destabilization of cyclin D1/p27KIP1 complexes.

CONCLUSIONS: These results highlight a mechanism of action of lenalidomide in MCL cases with increased tumorigenicity in vivo, which is mediated by the dissociation of cyclin D1/p27(KIP1) complexes, and subsequent proliferation blockade and apoptosis induction. PMID: 24178620 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Lenalidomide and Chronic Lymphocytic Leukemia.

Authors: González-Rodríguez AP, Payer AR, Acebes-Huerta A, Huergo-Zapico L, Villa-Alvarez M, Gonzalez-García E, Gonzalez S Abstract Lenalidomide is an oral immunomodulatory drug used in multiple myeloma and myelodysplastic syndrome and most recently it has shown to be effective in the treatment of various lymphoproliferative disorders such as chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma. The mechanism of action of lenalidomide varies depending on the pathology, and in the case of CLL, it appears to primarily act by restoring the damaged mechanisms of tumour immunosurveillance. This review discusses the potential mechanism of action and efficacy of lenalidomide, alone or in combination, in treatment of CLL and its toxic effects such as tumor lysis syndrome (TLS) an...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Long-term follow-up of lenalidomide in relapsed/refractory mantle cell lymphoma: subset analysis of the NHL-003 study

Conclusions These results show the activity of lenalidomide in heavily pretreated, relapsed/refractory MCL. Responders had a durable response with manageable side-effects. Clinical trial number posted on www.clinicaltrials.gov NCT00413036. (Source: Annals of Oncology)

Measuring cereblon as a biomarker of response or resistance to lenalidomide and pomalidomide requires use of standardized reagents and understanding of gene complexity

Summary Cereblon, a member of the cullin 4 ring ligase complex (CRL4), is the molecular target of the immunomodulatory drugs (IMiDs) lenalidomide and pomalidomide and is required for the antiproliferative activity of these agents in multiple myeloma (MM) and immunomodulatory activity in T cells. Cereblon's central role as a target of lenalidomide and pomalidomide suggests potential utility as a predictive biomarker of response or resistance to IMiD therapy. Our studies characterized a cereblon monoclonal antibody CRBN65, with high sensitivity and specificity in Western analysis and immunohistochemistry that is superior to commercially available antibodies. We identified multiple cereblon splice variants in both MM cell lines and primary cells, highlighting challenges with conventional gene...

Celgene raises 2013 forecast as profit beats estimates

(Reuters) - Celgene Corp raised its earnings forecast for 2013 on Thursday after reporting slightly higher-than-expected quarterly profit on robust sales of its flagship blood cancer drug Revlimid and rapid growth in newer cancer treatments. (Source: Reuters: Health)

Celgene profit tops Street view; raises 2013 forecast

(Reuters) - Celgene Corp on Thursday reported a slightly higher-than-expected third-quarter profit as sales of its flagship blood cancer drug Revlimid and of Abraxane for breast and lung cancer grew, and the company raised its 2013 earnings forecast. (Source: Reuters: Health)

Role of chemokines and their receptors in chronic lymphocytic leukemia: Function in microenvironment and targeted therapy.

Authors: Han TT, Fan L, Li JY, Xu W Abstract Chemokines produced in distinct tissue microenvironments sustain migration of mature lymphocytes in lymphoglandula. Chemokine receptors expressed on chronic lymphocytic leukemia (CLL) cells regulate the migration of the leukemia cells within the bone marrow (BM), lymphoid organs in collaboration with chemokines. Chemokines form a pro-survival circuitry by regulating leukocyte trafficking, maintaining extended lymphocyte survival. Therefore, chemokines in tumor cell-microenvironment interactions represent a target for treatment of CLL. AMD3100 disrupts the CLL/microenvironment interactions and influences CXCL12/CXCR4 survival signaling. Fostamatinib, ibrutinib, GS-1101 as B-cell receptor (BCR) related kinase inhibitors inhibit BCR- and ch...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Combined lenalidomide, low‚?źdose dexamethasone, and rituximab achieves durable responses in rituximab‚?źresistant indolent and mantle cell lymphomas

CONCLUSIONSThe combination of lenalidomide, low‚?źdose dexamethasone, and rituximab achieved high response rates with durable responses in patients with rituximab‚?źresistant, indolent B‚?źcell and mantle cell lymphomas. Overall response rate increased from 29% after two 28‚?źday cycles of lenalidomide and low‚?źdose dexamethasone to 58% after the addition of rituximab, suggesting that lenalidomide can overcome resistance to rituximab. Cancer 2013. ¬© 2013 American Cancer Society. (Source: Cancer)

Haematological cancer: A step before the next leap?

Nature Reviews Clinical Oncology 10, 610 (2013). doi:10.1038/nrclinonc.2013.181 Author: Ravi Vij The survival of patients with multiple myeloma has improved tremendously over the years. However, patients with disease that has relapsed and is refractory to thalidomide, lenalidomide and bortezomib have poor long-term outcomes. The novel immunomodulatory drug pomalidomide now offers a new therapeutic option for these patients. (Source: Nature Clinical Practice Oncology)

New drugs and targeted treatments in Hodgkin‚??s lymphoma

Abstract: New drugs are being developed in recent years that may change the handling of relapsed and refractory Hodgkin‚??s lymphoma patients. Brentuximab vedotin treatment has already been approved by the FDA; and other drugs are promising, such as histone deacetylase inhibitors, bendamustine, lenalidomide and m-TOR inhibitors. (Source: Cancer Treatment Reviews)

Single-Agent Lenalidomide in Patients With Mantle-Cell Lymphoma Who Relapsed or Progressed After or Were Refractory to Bortezomib: Phase II MCL-001 (EMERGE) Study [Hematologic Malignancy]

Conclusion The MCL-001 study demonstrated durable efficacy of lenalidomide with a predictable safety profile in heavily pretreated patients with MCL who had all relapsed or progressed after or were refractory to bortezomib. (Source: Journal of Clinical Oncology)

Pomalidomide

This spotlight review focuses on the second-generation immunomodulatory drug pomalidomide, which was recently approved by the US Food and Drug Administration. This drug was approved for patients with multiple myeloma who have received at least 2 prior therapies, including lenalidomide and bortezomib, and have demonstrated disease progression on or within 60 days of completion of the last therapy. This review focuses on the clinical trial data that led to approval and provides advice for treating physicians who are now prescribing this drug for patients. (Source: Blood)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Initial Treatment of Nontransplant Patients With Multiple Myeloma

During the last two decades, many steps forward have been made in the treatment of multiple myeloma (MM) thanks to the introduction of the novel agents thalidomide, lenalidomide, and bortezomib. Despite this, MM remains an incurable disease. Elderly patients (‚?•65 years) represent the majority of subjects. Differently from younger ( (Source: Seminars in Oncology)

Initial Treatment of Transplant Candidates With Multiple Myeloma

Over the last decade, thalidomide, bortezomib, and lenalidomide have been introduced into the armamentarium of myeloma therapies. These novel agents have improved the rate of complete remission both before and after autologous stem cell transplantation (ASCT) without substantially increasing toxicity, which has important implications as the achievement of high-quality responses is a significant prognostic factor for outcome. This review will focus on the most recent results of novel agent-based induction therapies, as well as on interesting developments in the transplant phase that are aimed at improving the results of conditioning regimens. (Source: Seminars in Oncology)

New Developments in Post-transplant Maintenance Treatment of Multiple Myeloma

Treatment of multiple myeloma (MM) has evolved significantly over the past two decades with high-dose chemotherapy and autologous stem cell transplant (ASCT), incorporating novel therapies such as proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs) during induction and post-transplant maintenance therapies. We reviewed the evolution of maintenance therapy from traditional chemotherapy, interferon (IFN), and prednisone to the current use of thalidomide, lenalidomide, and bortezomib in the post-transplant maintenance setting. Based on existing literature, either thalidomide or lenalidomide can be recommended for maintenance therapy post-transplant resulting in improved progression- free survival (PFS) and overall survival (OS). Thalidomide is less tolerated than lenalidomide and d...

Role of Consolidation Therapy in Transplant Eligible Multiple Myeloma Patients

The role of high-dose therapy and autologous stem-cell transplantation (ASCT) in the treatment of multiple myeloma (MM) has continued to evolve in recent years. The novel agents thalidomide, bortezomib, and lenalidomide have been successfully incorporated into induction therapy in preparation for ASCT and are currently being investigated also as post-ASCT consolidation and maintenance therapy. Consolidation treatment is generally short term and aims to increase the frequency and depth of response obtained with the previous treatment phases, including novel agent-based induction therapy and ASCT. This review will focus on recent trials of novel agents as post-ASCT consolidation therapy, offering an overview of pros and cons of this new treatment strategy in the ASCT sequence for MM patients...

Novel Generation of Agents With Proven Clinical Activity in Multiple Myeloma

The activity observed with proteasome inhibitors and immunomodulatory drugs (IMIDs) in multiple myeloma (MM) has prompted the development of second- and third-generation agents with similar, but not exactly the same, mechanisms of action as their predecessors. This review summarizes the mechanism of action and the available data on the clinical activity of novel proteasome inhibitors (carfilzomib, oprozomib, ixazomib, and marizomib) and novel IMIDs (pomalidomide), stressing the similarities and differences with bortezomib, and with thalidomide and lenalidomide, respectively. In summary, these novel agents have shown clinical activity as single agents and in combination with dexamethasone, with similar or even higher efficacy than their parental drugs; moreover, they may even overcome resis...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Novel Agents for Multiple Myeloma to Overcome Resistance in Phase III Clinical Trials

The incorporation of novel agents such as bortezomib and lenalidomide into initial therapy for multiple myeloma has improved the response rate of induction regimens. Also, these drugs are being increasingly used in the peri-transplant setting for transplant-eligible patients, and as part of consolidation and/or maintenance after front-line treatment, including in transplant-ineligible patients. Together, these and other strategies have contributed to a prolongation of progression-free survival (PFS) and overall survival (OS) in myeloma patients, and an increasing proportion are able to sustain a remission for many years. Despite these improvements, however, the vast majority of patients continue to suffer relapses, which suggests a prominent role for either primary, innate drug resistance,...

The Future of Drug Development and Therapy in Myeloma

The treatment options and outcomes for patients with myeloma has dramatically improved over the past decade, due in large part to the availability of improved anti-myeloma treatments including high-dose therapy, thalidomide, bortezomib, and lenalidomide. Many of the currently active agents are effective because of their impact on normal plasma cell biology, suggesting that targeting the plasma cell, rather than malignant cell biology has led to more effective therapy. Additionally, the use of combination therapy, with agents that are synergistic when combined, has led to deeper responses, and these have likely also contributed to improvements not only in progression free but also overall survival. With the wealth of new agents coming into the myeloma space, it is incumbent upon us as inves...

Multiple myeloma: from diagnosis to treatment.

DISCUSSION: Multiple myeloma can present with a wide constellation of symptoms including hypercalcaemia, anaemia, renal impairment and/or bony pain. A combination of these symptoms, particularly if unexpected or unexplained, should prompt diagnostic evaluation for myeloma. Work up of plasma cell disorders involves establishing the presence of a monoclonal paraprotein, baseline bloods and radiological investigations. Haematology referral is required for bone marrow biopsy and ongoing management. Newer treatments such as the immunomodulators thalidomide or lenalidomide, or the proteasome inhibitor bortezomib, administered in combination with steroids and occasionally cytotoxic agents have improved outcomes in patients with myeloma. Autologous stem cell transplant is offered to younger patien...

Lenalidomide induced photosensitivity

Summary Lenalidomide is an angiogenesis inhibitor and antitumoral drug approved to treat relapsed multiple myeloma, amyloidosis and myelodysplastic syndromes. Cutaneous side effects are a known complication of lenalidomide. We are going to report the first case of lenalidomide induced photosensitivity. (Source: Photodermatology, Photoimmunology and Photomedicine)

Continuous treatment in multiple myeloma: The future?

Abstract: Major therapeutic advances in the treatment of multiple myeloma (MM) have dramatically improved response rate, remission duration and overall survival. These advances include the introduction of high-dose therapy plus autologous stem cell transplantation in younger patients and, in more recent years, the use of ‚??novel‚?Ě agents such as Thalidomide, Bortezomib, and Lenalidomide.However, despite this progress, most patient will ultimately relapse and die from resistant disease.The role of maintenance therapy in MM has been investigated for more than 30years, but evidence of clear benefit has only recently emerged. The widely use of novel agents renewed the concept of maintenance or ‚??continuous‚?Ě treatment, after high dose therapy, as well as after conventional therapy in elder...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Treatment trade‚?źoffs in myeloma

CONCLUSIONSThe current results indicated that willingness to receive maintenance treatment declined when actual benefits were provided in concrete numeric terms compared with a general statement of PFS benefit. The authors also observed that the magnitude of benefit required to consider maintenance was affected by cost and toxicity. Cancer 2013. © 2013 American Cancer Society. (Source: Cancer)

Treatment trade‚?źoffs in myeloma: A survey of consecutive patients about contemporary maintenance strategies

CONCLUSIONSThe current results indicated that willingness to receive maintenance treatment declined when actual benefits were provided in concrete numeric terms compared with a general statement of PFS benefit. The authors also observed that the magnitude of benefit required to consider maintenance was affected by cost and toxicity. Cancer 2013;119:4308‚??4315. ¬© 2013 American Cancer Society. (Source: Cancer)

Recombinant thrombomodulin improved Stevens-Johnson syndrome with high serum high-mobility group-B1 DNA-binding protein induced by lenalidomide administered to treat multiple myeloma

Stevens-Johnson syndrome (SJS) is a serious adverse cutaneous reaction induced by drugs. The major clinical symptoms range from erythematous to dusky maculae, flat atypical targets, blisters on maculae, erosions and systemic symptoms . The approximate mortality rate of patients with SJS is 5% . Treatment for SJS has not yet been established, except for withdrawal of the causative drug. (Source: Thrombosis Research)

Long-term follow-up of lenalidomide in relapsed/refractory mantle cell lymphoma: subset analysis of the NHL-003 study.

CONCLUSIONS: These results show the activity of lenalidomide in heavily pretreated, relapsed/refractory MCL. Responders had a durable response with manageable side-effects. Clinical trial number posted on www.clinicaltrials.gov NCT00413036. PMID: 24030098 [PubMed - as supplied by publisher] (Source: Ann Oncol)

Phase II study of pegylated liposomal doxorubicin, low‚?źdose dexamethasone, and lenalidomide in patients with newly diagnosed multiple myeloma

ABSTRACT Our previous phase I/II trial of pegylated liposomal doxorubicin (PLD), low‚?źdose dexamethasone, and lenalidomide in patients with relapsed and refractory myeloma showed an overall response rate of 75%, with 29% achieving ‚?•VGPR. Here, we investigated this combination (PLD 30 or 40 mg/m2 intravenously, day 1; dexamethasone 40 mg orally, days 1‚?ź4; lenalidomide 25 mg orally, days 1‚?ź21; administered every 28 days) in a phase II study in patients with newly diagnosed symptomatic multiple myeloma to determine its efficacy and tolerability (ClinicalTrials.gov NCT00617591). At best response, patients could proceed with high‚?źdose melphalan or with maintenance lenalidomide and dexamethasone. In 57 patients, we found that the overall response rate and rate of very good partial respo...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Revlimid (Lenalidomide) for the Treatment of Mantle Cell Lymphoma (MCL)

Revlimid (lenalidomide) oral capsules are indicated for the treatment of Mantle Cell Lymphoma (MCL). (Source: Drug Development Technology)

Lenalidomide and low-dose dexamethasone for newly diagnosed primary plasma cell leukemia

Authors: P Musto, V Simeon, M C Martorelli, M T Petrucci, N Cascavilla, F Di Raimondo, T Caravita, F Morabito, M Offidani, A Olivieri, G Benevolo, R Mina, R Guariglia, G D'Arena, G Mansueto, N Filardi, F Nobile, A Levi, A Falcone, M Cavalli, G Pietrantuono, O Villani, S Bringhen, P Omed&#232;, R Lerose, L Agnelli, K Todoerti, A Neri, M Boccadoro & A Palumbo (Source: Leukemia)

Haematological cancer: Treatment of smoldering multiple myeloma

Nature Reviews Clinical Oncology 10, 554 (2013). doi:10.1038/nrclinonc.2013.160 Authors: S. Vincent Rajkumar & Robert A. Kyle In a recent randomized trial, lenalidomide plus low-dose dexamethasone prolonged overall survival in patients with high-risk smoldering multiple myeloma. Although the results are impressive, the generalizability is limited to a small subset of patients. Additional studies are needed to identify specific patient populations who can benefit from early intervention. (Source: Nature Clinical Practice Oncology)

NKT cell defects in multiple myeloma and the impact of lenalidomide therapy

Summary The causes of multiple myeloma (MM) remain obscure and there are few known risk factors, however NKT cell abnormalities have been reported in patients with MM, and therapeutic targeting of NKT cells is promoted as a potential treatment. We characterized NKT cell defects in treated and untreated patients with MM and determined the impact of lenalidomide therapy on the NKT cell pool. Lenalidomide is an immunomodulatory drug with co‚?źstimulatory effects on NKT cells in vitro and is an approved treatment for MM, although its mode of action in that context is not well defined. We find that patients with relapsed/progressive MM had a marked deficiency in NKT cell numbers. In contrast, newly diagnosed patients had relatively normal NKT cell frequency and function prior to treatment, alth...

How I treat patients with relapsed chronic lymphocytic leukaemia

Summary As front line therapy has improved, the treatment of relapsed chronic lymphocytic leukaemia has become more difficult as the disease becomes resistant and the patient accumulates comorbidities. The outcome for those who relapse after immunochemotherapy with fludarabine, cyclophosphamide and rituximab is strongly influenced by the duration of initial response. Patients who relapse within the first year or with a TP53 abnormality have very high‚?źrisk disease and will not respond to chemotherapy. High dose glucocorticoid and alemtuzumab followed by an allogeneic stem cell transplant is probably the best approach for younger, fitter patients in this category. Those who relapse after 2‚??3¬†years without TP53 abnormality will probably respond to their initial therapy again. Relapse wit...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Responsiveness of cytogenetically discrete human myeloma cell lines to lenalidomide: Lack of correlation with cereblon and interferon regulatory factor 4 expression levels

This article is protected by copyright. All rights reserved. (Source: European Journal of Haematology)

Decreased incidence of EPCR 4678G/C SNP in multiple myeloma patients with thrombosis

Patients with Multiple Myeloma (MM) have an increased risk of thrombosis . The underlying pathogenetic mechanism has not been fully elucidated. Several disease-specific factors have been implicated in the pathogenesis of hypercoagulation. Apart from non specific factors (age, immobility, comorbidities), qualitative and quantitative defects in coagulation and fibrinolytic factors, acquired protein C resistance, as well as high proinflammatory cytokine levels are considered as triggering factors . It is also well established that endothelial perturbing therapies, such us chemotherapy and immunomodulatory agents (thalidomide, lenalidomide), enhance the risk of thrombosis in patients with MM . Since classic inherited thrombophilia (FVLeiden 1691G/A, FII 20210G/A) has not been definitely proved...

Correction for Wei et al., A critical role for phosphatase haplodeficiency in the selective suppression of deletion 5q MDS by lenalidomide [Corrections]

MEDICAL SCIENCES Correction for ‚??A critical role for phosphatase haplodeficiency in the selective suppression of deletion 5q MDS by lenalidomide,‚?Ě by Sheng Wei, Xianghong Chen, Kathy Rocha, P. K. Epling-Burnette, Julie Y. Djeu, Qing Liu, John Byrd, Lubomir Sokol, Nick Lawrence, Roberta Pireddu, Gordon Dewald, Ann Williams, Jaroslaw Maciejewski, and... (Source: Proceedings of the National Academy of Sciences)

The combination of lenalidomide and dexamethasone reduces bone resorption in responding patients with relapsed/refractory multiple myeloma but has no effect on bone formation: Final results on 205 patients of the Greek Myeloma Study Group

Abstract The combination of lenalidomide plus dexamethasone (RD) is very effective for patients with relapsed/refractory myeloma. However, the effect of RD on bone metabolism has not been previously evaluated in these patients. To address this issue, we initially performed a retrospective study in 106 consecutive patients with relapsed or refractory myeloma who received RD. We measured the following bone indices on cycle 1/day 1 and then on cycles 3 and 6/day 28: dickkopf‚?ź1 (Dkk‚?ź1), sRANKL, osteoprotegerin (OPG), bone resorption markers (C‚?źtelopeptide of collagen type‚?źI, CTX and TRACP‚?ź5b) and bone formation markers (bone‚?źspecific alkaline phosphatase‚?źbALP and osteocalcin). RD produced a reduction of CTX only in responders, with no effect on bone formation. To validate these r...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Renal transplant in plasma cell dyscrasias with lenalidomide treatment after autologous stem cell transplantation

We report two cases of patients diagnosed with PCD undergoing renal transplantation after autologous stem cell transplantation, both cases under treatment with lenalidomide. We also report their perioperative management and their outcome. (Source: Nephrology)

Targeted Strategies in the Treatment of Primary Gastric Lymphomas: From Rituximab to Recent Insights into Potential New Drugs.

Authors: Merchionne F, Iacopino P, Minoia C, Iacobazzi A, Rana A, Serratńļ S, De Tullio G, Loseto G, Lapietra A, Lucarelli A, Guarini A Abstract Primary gastric non-Hodgkin's lymphomas (PG-NHL) are the most common extranodal lymphomas, representing between 47% and 74% of all gastrointestinal lymphoma cases. In Western countries two histological types, diffuse large B-cell (DLBC) NHL and mucosa-associated lymphoid tissue (MALT) NHL, are more frequently represented, accounting for the majority of gastric tumors after adenocarcinoma. For several years treatment of these PG lymphomas consisted of surgery, chemotherapy and radiotherapy, alone or in combination. In the last two decades however, advances in our understanding of their pathogenesis and biology have changed the treatment str...

Bortezomib induction, reduced-intensity transplantation, and lenalidomide consolidation-maintenance for myeloma: updated results

A sequential approach including bortezomib induction, intermediate-dose melphalan, and autologous stem cell transplantation (ASCT), followed by lenalidomide consolidation-maintenance, has been evaluated. Efficacy and safety data have been analyzed on intention-to-treat and results updated. Newly diagnosed myeloma patients 65 to 75 years of age (n = 102) received 4 cycles of bortezomib-pegylated liposomal doxorubicin-dexamethasone, tandem melphalan (100 mg/m2) followed by ASCT (MEL100-ASCT), 4 cycles of lenalidomide-prednisone consolidation (LP), and lenalidomide maintenance (L) until disease progression. The complete response (CR) rate was 33% after MEL100-ASCT, 48% after LP and 53% after L maintenance. After a median follow-up of 66 months, median time-to-progression (TTP) was 55 months a...

Current therapy of myelodysplastic syndromes

Abstract: After being a neglected and poorly-understood disorder for many years, there has been a recent explosion of data regarding the complex pathogenesis of myelodysplastic syndromes (MDS). On the therapeutic front, the approval of azacitidine, decitabine, and lenalidomide in the last decade was a major breakthrough. Nonetheless, the responses to these agents are limited and most patients progress within 2years. Allogeneic stem cell transplantation remains the only potentially curative therapy, but it is associated with significant toxicity and limited efficacy. Lack or loss of response after standard therapies is associated with dismal outcomes. Many unanswered questions remain regarding the optimal use of current therapies including patient selection, response prediction, therapy seq...

Synthesis and Stability of Oxetane Analogs of Thalidomide and Lenalidomide

Organic LettersDOI: 10.1021/ol401705a (Source: Organic Letters)

Lenalidomide Trial KO'd: A Blow to CLL Patients?Lenalidomide Trial KO'd: A Blow to CLL Patients?

Dr. Bruce Cheson discusses the clinical ramifications of the decision to halt the ORIGIN trial, which compared lenalidomide vs chlorambucil in previously untreated elderly patients with CLL. Medscape Oncology (Source: Medscape Today Headlines)

Pomalidomide Celgene¬ģ - (pomalidomide) licensed for use in the UK for the treatment of adults with relapsed/refractory multiple myeloma

Celgene has confirmed that Pomalidomide Celgene¬ģ - (pomalidomide), a new oral blood cancer therapy, has been granted Marketing Authorisation by the European Medicines Agency and is now available in the UK and Ireland. Pomalidomide is for use in combination with dexamethasone for the treatment of adults with relapsed and refractory multiple myeloma (rrMM) who have received at least two prior therapies including both lenalidomide and bortezomib, and have demonstrated disease progression while on their last therapy... (Source: Health News from Medical News Today)

Memory loss during lenalidomide treatment: a report on two cases

Conclusion: Lenalidomide may induce particular cognitive disorders (notably episodic memory impairments) in some patients. The drug's putative neurotoxicity is probably promoted by specific risk factors (such as previous chemotherapy, prior mild cognitive impairment, age and the presence of cerebrovascular lesions). (Source: BMC Clinical Pharmacology)

Trends in Utilization and Outcomes of Autologous Transplantation as Early Therapy for Multiple Myeloma

Abstract: The impact of novel drugs for treating multiple myeloma (MM) on the utilization and outcomes of autologous hematopoietic progenitor cell transplantation (AHPCT) is unknown. We reviewed characteristics and outcomes of 20,278 patients who underwent AHPCT within 12 months of diagnosis of MM in the United States and Canada and registered at the Center for International Blood and Marrow Transplant Research (CIBMTR) in 3 time cohorts reflecting the increasing availability of novel drugs: 1995 to 1999 (n = 2226), 2000 to 2004 (n = 6408), and 2005 to 2010 (n = 11,644). In the United States, the number of AHPCTs performed increased at a greater rate than new MM cases. Patients in recent cohorts were older, less likely to have stage 3 MM, and more likely to have received previous t...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Targeting inflammatory pathways in chronic lymphocytic leukemia

Abstract: Despite recent major advances in leukemia research, the pathobiology of chronic lymphocytic leukemia (CLL) remains poorly understood. Herein we review the role chronic inflammation plays in the initiation and progression of CLL. The robust production of inflammatory cytokines and chemokines accompanied by activation of intra-cellular pro-inflammatory pathways, and the presence of somatic mutations that activate pro-inflammatory signaling pathways, suggest that chronic inflammation plays a pathophysiological role in this disease. Indeed, glucocorticoids and non-steroidal anti-inflammatory possess anti-tumor activity, and glucocorticoids have been broadly used to treat CLL and its complications. Recent clinical trials demonstrated that tyrosine kinase inhibitors, such as ibrutinib ...

Immunomodulation therapy with lenalidomide in follicular, transformed and diffuse large B cell lymphoma: current data on safety and efficacy

Lenalidomide is an immunomodulatory agent which has been approved for multiple myeloma. Lenalidomide is also effective in and tolerated well by patients with follicular lymphoma, diffuse large B-cell lymphoma, and transformed large cell lymphoma. This review summarizes the results of current preclinical and clinical studies of lenalidomide, alone or in combination with the monoclonal antibody rituximab, as a therapeutic option for these three lymphoma types. This review will serve as a tool guiding future clinical investigations to improve survival rates for these three lymphomas. (Source: Journal of Hematology and Oncology)

Early Myeloma Treatment Slows Progression (CME/CE)

(MedPage Today) -- Patients treated with standard care for smoldering myeloma -- observation until symptoms develop -- had worse outcomes than early lenalidomide plus dexamethasone treatment, researchers found. (Source: MedPage Today Hematology/Oncology)

Lenalidomide induces long-lasting responses in elderly patients with chronic lymphocytic leukemia

We evaluated long-term outcomes of 60 patients with chronic lymphocytic leukemia treated with an initial therapy of lenalidomide. At a median follow-up of 4 years, time-to-treatment failure has not been reached and overall survival is 82%. Thirty-five (58%) patients had a response lasting &gt;36 months (long-term responders [LTRs]). Best LTR responses consisted of 25 (71%) complete remissions and 10 (29%) partial remissions. In addition to clinical responses, an increase in IgA, IgG, and IgM levels of &gt;50% from baseline was reported in 61%, 45%, and 42% of LTRs. Normalization in the percentage of CD4+ and CD8+ cells and T-cell numbers was observed in 48%, 71% and 99% of LTRs. Compared with other patients in the study, LTRs had lower baseline plasma levels of &beta;-2-microglobulin, were...

Lenalidomide plus Dexamethasone for High-Risk Smoldering Multiple Myeloma

New England Journal of Medicine, Volume 369, Issue 5, Page 438-447, August 2013. (Source: New England Journal of Medicine)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Early Treatment of High-Risk Smoldering Multiple Myeloma Improves Outcomes

Early treatment with lenalidomide and dexamethasone in patients with high-risk smoldering myeloma significantly delayed progression to symptomatic disease and prolonged survival with a good safety profile. (Source: Cancer Network)

[News] Lenalidomide as first-line therapy for elderly CLL patients

Two-thirds of all patients who are newly diagnosed with chronic lymphocytic leukaemia (CLL) are older than 65 years, but these individuals are infrequently represented in clinical trials. No consensus exists on the best first-line therapy for CLL in elderly patients, a population who often experience treatment-limiting toxicities with the therapeutic regimens that are effective in younger patients. (Source: The Lancet Oncology)

Screening Thalidomide analogs in vivo and in vitro [Developmental Biology]

Thalidomide and its analog, Lenalidomide, are in current use clinically for treatment of multiple myeloma, complications of leprosy and cancers. An additional analog, Pomalidomide, has recently been licensed for treatment of multiple myeloma, and is purported to be clinically more potent than either Thalidomide or Lenalidomide. Using a combination of... (Source: Proceedings of the National Academy of Sciences)

5q‚?? syndrome and multiple myeloma diagnosed simultaneously and successful treated with lenalidomide

Abstract: A 72-year-old woman was diagnosed with 5q‚?? myelodysplastic syndrome in the course of an indolent multiple myeloma (MM). Bone marrow (BM) cytogenetics disclosed two unrelated clones: 46,XX,del(5)(q13q33), and [47,X,-X,der(1;21)(q10;q10),‚??4,‚??4,+5,del(5)(q13q31),+7,der(7)t(1;7)(p34.2;p22),add(8)(p23),‚??13,+15,der(16) t(1;16)(q23;q12.2),+19,‚??21,+mar1,+mar2]. The last complex karyotype belonged to malignant plasma cells. FISH and SKY techniques demonstrated different 5q deletions. EGR1 gene (on 5q31) lost in 5q‚?? syndrome remained in 5q‚?? plasma cells. Biclonal evolution was noted: myeloid 5q‚?? cells added a deletion 13q and plasma cells showed monosomy 13. Patient achieved complete cytogenetic response of 5q‚?? syndrome with low-dose of lenalidomide, and a partial remissi...

Minimal Change Disease and Lenalidomide

A 48-year-old man who had been diagnosed 2 years earlier with Waldenström macroglobulinemia was admitted with nephrotic syndrome. Previously, partial remission had been achieved following treatment with a combination of rituximab, dexamethasone, and cyclophosphamide for 6 months. Fatigue recurred 4 months prior to admission. Serum protein electrophoresis revealed 30 g/L of immunoglobulin M (IgM), and he was started on lenalidomide treatment. At this time, protein was undetectable by dipstick urine test. Three weeks later, the patient abruptly developed signs of nephrotic syndrome: a rapid increase in body weight, peripheral edema, and foamy urine containing 20 g/L of protein that consisted mainly of albumin (97%). Urinary sediment was inactive. A subsequent kidney biopsy showed no histolo...

Evidence of a role for CD44 and cell adhesion in mediating resistance to lenalidomide in multiple myeloma: therapeutic implications

Authors: C C Bjorklund, V Baladandayuthapani, H Y Lin, R J Jones, I Kuiatse, H Wang, J Yang, J J Shah, S K Thomas, M Wang, D M Weber & R Z Orlowski (Source: Leukemia)

Celgene raises full-year outlook on strong cancer drug sales

(Reuters) - Biotechnology firm Celgene Corp raised its full-year earnings forecast for the second time in three months after it reported a quarterly profit above analysts' estimates, as its cancer drugs, Revlimid and Abraxane, continued to post strong sales growth. (Source: Reuters: Health)

Lenalidomide Leukemia Clinical Trial StoppedLenalidomide Leukemia Clinical Trial Stopped

A phase 3 trial exploring the use of lenalidomide (Revlimid) in chronic lymphocytic leukemia has been stopped after safety concerns. Medscape Medical News (Source: Medscape Today Headlines)

Combination of intravenous immunoglobulins and lenalidomide in the treatment of scleromyxedema

To the Editor: The dermatology service was consulted to review the case of a 44-year-old man, who presented to the hospital with a 2-year history of papulonodular lesions associated with skin thickening. The eruption, initially located on the face and neck, had recently spread to the extremities and folds (). The clinical presentation was consistent with scleromyxedema and this diagnosis was confirmed by the histopathologic study. Serum protein electrophoresis with immunofixation showed evidence of a lambda light chain monoclonal gammopathy, but all other laboratory tests, including autoimmune and thyroid markers as well as blood glucose, were nonreactive and within normal limits, respectively. HIV testing was negative. Bone marrow analysis confirmed the diagnosis of monoclonal gammopathy ...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Deaths Halt Revlimid Leukemia Trial

(MedPage Today) -- The FDA has discontinued a phase III trial evaluating the investigational use of lenalidomide (Revlimid) for older patients with B-cell chronic lymphocytic leukemia because of an excess risk of death. (Source: MedPage Today Geriatrics)

Trial of Blood Cancer Drug Halted Because of Increased Mortality Risk (FREE)

By Kelly Young The FDA has halted a phase III trial of lenalidomide (Revlimid) after an increased mortality risk was observed, the manufacturer announced ‚?¶ (Source: Physician's First Watch current issue)

Celgene to terminate Phase III ORIGIN trial of Revlimid

Celgene has decided to terminate the Phase III ORIGIN trial of Revlimid (lenalidomide) due to imbalance in the number of deaths in lenalidomide patient-group compared to patients treated with chlorambucil. (Source: Drug Development Technology)

Celgene to stop blood cancer trial due to high death rates

(Reuters) - Celgene Corp said it will stop a late-stage trial of its blood cancer drug Revlimid after it observed a higher number of deaths in patients taking the drug compared to those on another treatment. (Source: Reuters: Health)

Revised International Prognostic Scoring System (IPSS) Predicts Survival and Leukemic Evolution of Myelodysplastic Syndromes Significantly Better Than IPSS and WHO Prognostic Scoring System: Validation by the Gruppo Romano Mielodisplasie Italian Regional Database [Hematologic Malignancies]

Conclusion Our data confirm that the IPSS-R is an excellent prognostic tool in MDS in the era of disease-modifying treatments. The early recognition of patients at high risk of progression to aggressive disease may optimize treatment timing in MDS. (Source: Journal of Clinical Oncology)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Review of health-related quality of life data in multiple myeloma patients treated with novel agents

Authors: P Sonneveld, S G Verelst, P Lewis, V Gray-Schopfer, A Hutchings, A Nixon & M T Petrucci (Source: Leukemia)

Celgene's Phase III study of oral Revlimid meets primary endpoint

Celgene International's Phase III study (MM-020/IFM 07-01) of oral Revlimid (Lenalidomide) in combination with low-dose dexamethasone (Rd) has met its primary endpoint of progression-free survival (PFS) in patients newly diagnosed with multiple myelo‚?¶ (Source: Drug Development Technology)

"Revlimid" A Step Closer To Being Approved For New Cases Of Multiple Myeloma

Celgene Corp's cancer drug Revlimid (lenalidomide) met its main goal in the drug's phase III late-stage trial, meaning that the medication is one step closer to being approved for new cases of multiple myeloma. Multiple myeloma is also known as plasma cell myeloma. It is a form of cancer that affects the plasma cells - white blood cells found in the bone marrow. Plasma cells are important because they help produce antibodies which fight off infections. According to the American Cancer Society there will be around 22,350 new cases of multiple myeloma this year and over 10,000 deaths... (Source: Health News from Medical News Today)

Market for Celgene blood cancer drug seen growing after trial

(Reuters) - Celgene Corp said a late-stage trial of its cancer drug Revlimid met the main goal of improving survival in newly diagnosed blood cancer patients, potentially opening up the path for a wider use of the drug. (Source: Reuters: Health)

Celgene's Revlimid improves survival in blood cancer patients

(Reuters) - Celgene Corp said a late-stage trial of its cancer drug Revlimid met the main goal of improving survival in blood cancer patients. (Source: Reuters: Health)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

UK cost agency says 'no' to Celgene bone marrow drug

LONDON (Reuters) - Celgene's drug Revlimid is not worth using on Britain's state health service because of uncertainty over whether it can extend the lives of patients with serious bone marrow disorders, the country's cost agency said on Thursday. (Source: Reuters: Health)

Flavopiridol: Judged by the company one keeps

While CLL is an indolent lymphoproliferative disorder for many, patients refractory to chemotherapy or whose disease contains high-risk features, most notably dysfunctional p53 and ATM genes, continue to have an inferior prognosis. Agents such as lenalidomide, alemtuzumab and high-dose methylprednisolone have demonstrated improved response rates compared to standard chemotherapeutics albeit with limited durations of response. Allogeneic stem cell transplantation remains a relatively limited option in the treatment of CLL owing to the associated toxicity. (Source: Leukemia Research)

Single‚?źagent lenalidomide is active in patients with relapsed or refractory aggressive non‚?źhodgkin lymphoma who received prior stem cell transplantation

Summary Patients with aggressive non‚?źHodgkin lymphoma (NHL) who relapse after autologous stem cell transplantation (ASCT) have a poor prognosis. Additional therapy is often poorly tolerated, and new treatment modalities are needed. This efficacy and safety study was a retrospective analysis of two phase II trials (NHL‚?ź002 and NHL‚?ź003) that studied single‚?źagent lenalidomide in patients with relapsed/refractory aggressive NHL with prior (n¬†=¬†87) compared with no prior ASCT (n¬†=¬†179). The overall response rate in the ASCT group was 39% [14% complete response (CR)], including 29% in patients with diffuse large B‚?źcell lymphoma, 63% in mantle cell lymphoma, and 60% in transformed lymphoma. The timing of transplant relative to receiving lenalidomide had no effect on outcomes. Median...

Lenalidomide enhances the protective effect of a therapeutic vaccine and reverses immune suppression in mice bearing established lymphomas

Authors: I Sakamaki, L W Kwak, S-c Cha, Q Yi, B Lerman, J Chen, S Surapaneni, S Bateman & H Qin (Source: Leukemia)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Flow cytometry based enumeration and functional characterization of CD8 T regulatory cells in patients with multiple myeloma before and after lenalidomide plus dexamethasone treatment

ConclusionUsing flow cytometry, we have shown that suppressive CD8 Treg cells are increased in MM patients and len‚?źdex treatment is unable to control these suppressive CD8 Treg cells. ¬© 2013 Clinical Cytometry Society (Source: Cytometry Part B: Clinical Cytometry)

[Review of evidence of thalidomide and lenalidomide in different hematological diseases: chronic lymphocytic leukemia, primary amyloidosis, myelofibrosis and syndrome myelodysplastic.]

Authors: Jiménez Lozano I, Juárez Jiménez JC Abstract Lenalidomide is an immunomodulatory drug approved by the AEMPS and the EMA, in combination with dexamethasone, for the treatment of multiple myeloma in adult patients who have received at least one prior therapy. Moreover, it has recently been approved for the treatment of patients with transfusion-dependent anaemia due to low- or intermediate-1-risk myelodysplastic syndromes associated with an isolated deletion 5q cytogenetic abnormality when other therapeutic options are insufficient or inadequate. It has also shown to be active in other hematologic and no hematologic diseases. Growing evidence of its use entails a challenge when situating the drug in a cost-effective way to treat these diseases. On this article we review t...

Very long‚?źlasting remission of refractory T‚?źlarge granular lymphocytes leukemia and myeloma by lenalidomide treatment

ConclusionsAs far as we know, this is the first report of a patient with refractory T‚?źLGLL treated with bortezomib and lenalidomide. As refractory T‚?źLGLL is a challenging condition, we think that lenalidomide and bortezomib deserve further investigation. (Source: European Journal of Haematology)

Lenalidomide plus cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab is safe and effective in untreated elderly diffuse large B-cell lymphoma patients: phase I study by the Fondazione Italiana Linfomi.

Authors: Chiappella A, Tucci A, Castellino A, Pavone V, Baldi I, Carella AM, Orsucci L, Zanni M, Salvi F, Liberati AM, Gaidano G, Bottelli C, Rossini B, Perticone S, De Masi P, Ladetto M, Ciccone G, Palumbo A, Rossi G, Vitolo U Abstract Despite improvements in standard therapy with rituximab-cyclophosphamide-doxorubicin- vincristine-prednisone scheme for patients with untreated, diffuse large-B-cell lymphoma up to 40% relapse. Lenalidomide alone or in combination with rituximab showed activity in relapsed/refractory aggressive lymphomas. In this phase I study we determined the maximum tolerated dose of lenalidomide plus rituximab-cyclophosphamide-doxorubicin-vincristine- prednisone in untreated elderly (median age 68 years) patients with diffuse large-B-cell lymphoma. Four lenalido...

Sequence of novel agents in multiple myeloma: An instrumental variable analysis

Abstract: Lenalidomide and bortezomib have not been compared prospectively and are currently used in sequence for patients with multiple myeloma; however, it is unknown whether a sequence of administration could result in improved outcomes. We retrospectively reviewed electronic records of patients with multiple myeloma who had used both agents in sequence at our institution: 97 patients had lenalidomide first and 111 had bortezomib first. On multivariable analysis, the sequence of therapy was not associated with outcome. These findings were confirmed with instrumental variable analyses. Finally, use of bortezomib first was associated with improved survival for patients with baseline renal insufficiency. (Source: Leukemia Research)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Divergent Effects of Novel Immunomodulatory Agents and Cyclophosphamide on the Risk of Engraftment Syndrome after Autologous Peripheral Blood Stem Cell Transplantation for Multiple Myeloma

In this study, we demonstrate that the incidence of ES is significantly increased in patients undergoing autologous PBSCT for multiple myeloma in comparison to patients with non-Hodgkin lymphoma or Hodgkin lymphoma. Multivariate analysis revealed that age > 60 (hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.12 to 2.62; P = .013) and transplantation for multiple myeloma (HR, 2.80; 95% CI, 1.60 to 4.90; P = .0003) were associated with an increased risk of this complication. When stratified for myeloma patients only, age > 60 (HR, 1.80; 95% CI, 1.13 to 2.87; P = .013) and prior treatment with both lenalidomide and bortezomib (HR, 1.83; 95% CI, 1.11 to 3.04; P = .0001) were associated with an increased incidence of ES. Conversely, lack of exposure to cyclophosphamide from either ...

Waldenström macroglobulinemia: 2013 update on diagnosis, risk stratification, and management

Disease OverviewWaldenstr√∂m macroglobulinemia (WM) is a lymphoplasmacytic lymphoma with immunoglobulin M (IgM) monoclonal protein. Clinical features include anemia, thrombocytopenia, hepatosplenomegaly, and lymphadenopathy. DiagnosisThe presence of IgM monoclonal protein associated with ‚?•10% clonal lymphoplasmacytic cells in bone marrow confirms the diagnosis. Risk StratificationAge, hemoglobin level, platelet count, ő≤2 microglobulin, and monoclonal IgM concentrations are characteristics required for prognosis. Risk‚?źAdapted TherapyNot all patients who fulfill WM criteria require therapy; these patients can be observed until symptoms develop. Rituximab‚?źbased therapy is used in virtually all US patients with WM and can be combined with alkylating agent or purine nucleoside analog (or...

Lenalidomide at Therapeutic and Supratherapeutic Doses Does Not Prolong QTc Intervals in the Thorough QTc Study Conducted in Healthy Men

In conclusion, single doses of lenalidomide up to 50¬†mg were not associated with prolonged QTc intervals in healthy males. The C‚??QTc analysis further assured that lenalidomide doses up to 50¬†mg are not expected to prolong QTc intervals in patients. (Source: Basic and Clinical Pharmacology and Toxicology)

Revlimid¬ģ indicated as a treatment for patients with rare form of blood disease

Celgene International S√†rl (NASDAQ: CELG) has been notified that the European Commission (EC) has amended the marketing authorisation for REVLIMID¬ģ. This decision means that REVLIMID is now approved to treat patients with transfusion-dependent anaemia due to low or intermediate-1 risk myelodysplastic syndromes (MDS) associated with an isolated deletion 5q cytogenetic abnormality when other therapeutic options are insufficient or inadequate. (Source: Pharmacy Europe)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

A multicenter, open-label, phase 2 study of lenalidomide plus low-dose dexamethasone in Chinese patients with relapsed/refractory multiple myeloma: the MM-021 trial

Conclusions: Lenalidomide plus low-dose dexamethasone was associated with a high response rate and acceptable safety profile in heavily pretreated Chinese patients with RRMM, including those with renal impairment and IgD subtype. These findings highlight the clinical potential of this regimen in Chinese RRMM patients who have exhausted current treatment options.Trial registration: China State Food and Drug Administration (SFDA) registration (CTA reference numbers: 209 L10808; 209 L10809; 209 L10810; and 209 L10811) and ClinicalTrials.gov identifier: NCT01593410. (Source: Journal of Hematology and Oncology)

Factors affecting successful mobilization with plerixafor: an Italian prospective survey in 215 patients with multiple myeloma and lymphoma.

CONCLUSION: This large, prospective, nationwide study confirmed plerixafor efficacy for mobilizing PBSCs when added to G-CSF‚??with or without chemotherapy. Plerixafor can overcome negative effects of most predictors of poor mobilization to achieve satisfactory harvest both in predicted and proven PM. PMID: 23781769 [PubMed - as supplied by publisher] (Source: Transfusion)

Histone Deacetylase Inhibitors in Multiple Myeloma: Rationale and Evidence for Their Use in Combination Therapy.

Authors: Kaufman JL, Fabre C, Lonial S, Richardson PG Abstract Multiple myeloma (MM) arises from abnormal proliferation and survival (ie, a high proliferative index and a low apoptotic index) of mature immunoglobulin-producing plasma cells in the bone marrow. Development of novel therapeutic options, such as proteasome inhibitors and immunomodulatory agents (IMiDs), has improved treatment outcomes. However, patients often develop relapsed and refractory MM, thus requiring alternative treatment approaches. Histone acetyltransferases and histone deacetylases (HDACs) control the acetylation status of proteins and affect a broad array of physiologic processes (eg, cell cycle, apoptosis, and protein folding) involved in cell growth and survival. The discovery that HDACs might have a rol...

Phase I dose escalation study of bortezomib in combination with lenalidomide in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML)

Abstract: We conducted a phase I dose escalation study to determine the maximal tolerated dose of bortezomib that could be combined with standard dose lenalidomide in patients with MDS or AML. Treatment consisted of bortezomib (IV) on Days 1, 4, 8, and 11 and lenalidomide 10mg daily (PO) days 1‚??21 in 28 day cycles for up to 9 cycles. 23 patients (14 MDS/CMML, 9 AML) were enrolled. The maximally tested dose of bortezomib, 1.3mg/m2, was tolerable in this regimen. Responses were seen in patients with MDS and AML. Further testing of this regimen is planned. (Source: Leukemia Research)

Clinical and genetic factors associated with venous thromboembolism in myeloma patients treated with lenalidomide‚?źbased regimens

Conclusions: our data indicated that LMWH or vitamin K antagonists (with a target INR 2‚?ź3) effectively reduce the risk of VTEs. In patients who received prophylaxis with aspirin genetic variants of genes that are involved directly or indirectly in inflammatory response may be associated with increased risk of VTE. (Source: American Journal of Hematology)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

US FDA approves REVLIMID

Celgene Corporation (NASDAQ: CELG) today announced the U.S. Food and Drug Administration (FDA) has approved the company‚??s supplemental new drug application (sNDA) for REVLIMID¬ģ (lenalidomide) for the treatment of patients with mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib. (Source: Pharmacy Europe)

Risk factors for MDS and acute leukemia following total therapy 2 and 3 for multiple myeloma

Lenalidomide has been linked to myelodysplastic syndrome (MDS) after autotransplants for myeloma. Total therapy trials (TT; TT2&ndash;/+ thalidomide) and TT3 (TT3a with bortezomib, thalidomide; TT3b with additional lenalidomide) offered the opportunity to examine the contribution of these immune-modulatory agents to MDS-associated cytogenetic abnormalities (MDS-CA) and clinical MDS or acute leukemia ("clinical MDS/AL"). Of 1080 patients with serial cytogenetic studies, MDS-CA occurred in 11% and clinical MDS/AL in 3%. Risk features of MDS-CA included TT3b, age &ge;65 years, male gender, levels of &beta;-2-microglobulin &gt;5.5 mg/L, and multiple myeloma relapse. Clinical MDS/AL occurred less frequently in the control arm of TT2 and more often with TT3a and TT3b. Since MDS-CA often antedate...

FDA Approves Revlimid for Mantle Cell LymphomaFDA Approves Revlimid for Mantle Cell Lymphoma

It is only the second drug ever approved for this rare cancer. FDA Approvals (Source: Medscape Medical News Headlines)

Celgene's Revlimid wins FDA lymphoma approval

(Reuters) - Celgene Corp said on Wednesday that its flagship blood cancer drug, Revlimid, was approved by U.S. health regulators to treat mantle cell lymphoma, adding another revenue source for the $4 billion-a-year medicine. (Source: Reuters: Health)

A phase 2, multicentre, single-arm, open-label study to evaluate the safety and efficacy of single-agent lenalidomide (Revlimid¬ģ) in subjects with relapsed or refractory peripheral T-cell non-Hodgkin lymphoma: The EXPECT trial

This study was registered with ClinicalTrials.gov, number NCT00655668.Findings: A total of 54 patients with PTCL were treated. The overall response rate was 22% (12 of 54), including complete response (CR) or unconfirmed CR (CRu) in 11% of patients; 31% of patients with angioimmunoblastic T-cell lymphoma (AITL) responded (CR/CRu in 15% of patients). The median progression-free survival and median response duration were 2.5 and 3.6months, respectively, in the intent-to-treat population, and 4.6 and 3.5months, respectively, in patients with AITL. Thrombocytopenia and neutropenia were the most common grade 3 or 4 haematological AEs, in 11 (20%) and 8 (15%) patients, respectively. Overall, 19 patients (35%) experienced at least 1AE leading to study dose interruption or reduction (commonly neut...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Chronic lymphocytic leukemia: 2013 update on diagnosis, risk stratification and treatment

Abstract Disease OverviewChronic lymphocytic leukemia (CLL) is the commonest leukemia in western countries. The disease typically occurs in elderly patients and has a highly variable clinical course. Leukemic transformation is initiated by specific genomic alterations that impair apoptosis of clonal B‚?źcells. DiagnosisThe diagnosis is established by blood counts, blood smears, and immunophenotyping of circulating B‚?źlymphocytes, which identify a clonal B‚?źcell population carrying the CD5 antigen as well as B‚?źcell markers. PrognosisTwo prognostic staging systems exist, the Rai and Binet staging systems, which are established by physical examination and blood counts. Various biological and genetic markers also have prognostic value. Deletions of the short arm of chromosome 17 (del(17p))...

Multiple Myeloma Treatment Transformed: A Population-Based Study of Changes in Initial Management Approaches in the United States [Hematologic Malignancies]

Conclusion Initial treatment for multiple myeloma has changed markedly. Most patients now receive novel agents, with a decline in the use of traditional chemotherapy. Use of transplantation and novel agents varies with race and insurance. These findings document rapid changes in patterns of care and highlight addressable disparities in myeloma care. (Source: Journal of Clinical Oncology)

Combination of Azacitidine and Lenalidomide in Myelodysplastic Syndromes or acute Myeloid Leukemia‚??a wise Liaison?

Combination of Azacitidine and Lenalidomide in Myelodysplastic Syndromes or acute Myeloid Leukemia&#8212;a wise Liaison&#63; Leukemia advance online publication, May 28 2013. doi:10.1038/leu.2013.140 Authors: U Platzbecker & U Germing (Source: Leukemia)

Long-term outcome with lenalidomide and dexamethasone therapy for newly diagnosed multiple myeloma

Authors: G Srivastava, V Rana, M Q Lacy, F K Buadi, S R Hayman, A Dispenzieri, M A Gertz, D Dingli, S Zeldenrust, S Russell, A McCurdy, P Kapoor, R Kyle, S V Rajkumar & S Kumar (Source: Leukemia)

Mesenchymal stromal cells from patients with myelodyplastic syndromedisplay distinct functional alterations that are modulated by lenalidomide.

In conclusion, our analyses support the notion that the stromal microenvironment is involved in the pathophysiology of myelodysplastic syndrome thus representing a potential target for therapeutic interventions. PMID: 23716561 [PubMed - as supplied by publisher] (Source: Haematologica)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Phase 2 study of bortezomib-dexamethasone alone or with added cyclophosphamide or lenalidomide for sub-optimal response as second-line treatment for patients with multiple myeloma.

Authors: Dimopoulos MA, Beksac M, Benboubker L, Roddie H, Allietta N, Broer E, Couturier C, Mazier MA, Angermund R, Facon T Abstract In this phase 2 study, the first prospective evaluation of bortezomib-dexamethasone as second-line therapy for relapsed/refractory multiple myeloma, 163 patients were enrolled to receive four cycles of bortezomib-dexamethasone. Patients were investigator-assessed for response at cycle 5 day 1, then treated as follows: responding patients received another four cycles of bortezomib-dexamethasone, while patients with stable disease were subsequently randomized to sequential treatment with a further four cycles of bortezomib-dexamethasone alone or with added cyclophosphamide or lenalidomide. The primary endpoint was response to sequential therapy; however...

Lenalidomide, melphalan and dexamethasone in an immunoglobulin light chain amyloidosis patient population with high rates of advanced cardiac involvement.

Authors: Dinner S, Witteles W, Afghahi A, Witteles R, Arai S, Lafayette R, Schrier S, Liedtke M Abstract Immunoglobulin light chain amyloidosis remains incurable despite recent therapeutic advances, and is particularly difficult to treat in patients with amyloid cardiomyopathy. Based on evidence of activity in multiple myeloma, we designed a pilot study of an oral regimen of lenalidomide in combination with dexamethasone and low dose melphalan in order to evaluate its safety and efficacy in patients with amyloidosis, including those with advanced cardiac involvement. Twenty-five patients were enrolled. Ninety-two percent of patients had cardiac involvement by amyloidosis, and 36% of patients met criteria for Mayo Clinic cardiac stage III disease. Patients received up to 9 cycles of...

Disseminated keratotic spicules: A rare manifestation in multiple myeloma and successful response to lenalidomide

We describe one of the very few cases presenting with a generalized distribution and report the successful treatment with lenalidomide. (Source: Journal of the American Academy of Dermatology)

How we treat lower-risk myelodysplastic syndromes

Lower-risk myelodysplastic syndromes (MDSs) are defined as having low or intermediate 1 risk by the International Prognostic Scoring System and are characterized mainly by anemia in most cases. Supportive care&mdash;primarily red blood cell transfusions&mdash;remains an important component of their treatment, but exposes patients to insufficient correction of anemia, alloimmunization, and organ iron overload (for which the role of iron chelation remains debated). Treatment aimed at preventing anemia recurrence should therefore be used whenever possible. Erythropoiesis stimulating agents remain the first-line treatment of anemia in most lower-risk MDS without del(5q), whereas anemia of low-risk MDS with del 5q responds to lenalidomide in two-thirds of the cases, but this drug should be used...

Lenalidomide, Bendamustine and Prednisolone exhibits a favourable safety and efficacy profile in relapsed or refractory multiple myeloma: final results of a phase 1 clinical trial OSHO ‚?? #077

In conclusion, RBP with lenalidomide 25¬†mg/d, days 1‚??21 and bendamustine 75¬†mg/m2 days 1‚??2 is well tolerated in patients with relapsed/refractory MM. (Source: British Journal of Haematology)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Very long lasting remission of refractory T‚?źLarge Granular Lymphocytes Leukemia and myeloma by lenalidomide treatment

ConclusionsAs far as we know this is the first report of a patient with refractory T‚?źLGLL treated with bortezomib and lenalidomide. Since refractory T‚?źLGLL is a challenging condition we think that lenalidomide and bortezomib deserve further investigation.This article is protected by copyright. All rights reserved. (Source: European Journal of Haematology)

Polyclonal immune activation and marrow plasmacytosis in multiple myeloma patients receiving long-term lenalidomide therapy: incidence and prognostic significance

Authors: D Zamarin, S M Devlin, M E Arcila, H Landau, A Lesokhin, N Lendvai, D J Chung, D Chimento, J Weltz, D Babu, S Giralt & H Hassoun (Source: Leukemia)

Long-term repair of T-cell synapse activity in a phase II trial of chemoimmunotherapy followed by lenalidomide consolidation in previously untreated chronic lymphocytic leukemia (CLL)

Immunotherapy that facilitates endogenous T-cell activity has the potential to target therapy-resistant tumor clones. In vitro studies have demonstrated that lenalidomide repairs the T-cell immunologic synapse defect in chronic lymphocytic leukemia (CLL). Pentostatin, cyclophosphamide, and rituximab (PCR) in CLL is clinically active with modest toxicity, indicating suitability of this chemoimmunotherapy (CIT) platform for combination with immunotherapy. Here we report on a trial of PCR followed by lenalidomide consolidation. Of 34 patients who received lenalidomide, 24% improved their quality of response and 4 patients converted to minimal residual disease negative status. Retrospective comparison to a historical PCR trial indicated that lenalidomide consolidation extends time to progressi...

Novel agents for chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is a heterogeneous group of B-cell neoplasm. CLL is typically sensitive to a variety of cytotoxic agents, but relapse frequently occurs with conventional approaches. The treatment of CLL is evolving rapidly with the introduction of novel drugs, such as bendamustine, ofatumumab, lenalidomide, ibrutinib, idelalisib, veltuzumab, XmAb5574, navitoclax, dasatinib, alvespimycin, and TRU-016. This review summarizes the most current clinical experiences with these agents in the treatment of CLL. (Source: Journal of Hematology and Oncology)

Risk of second primary malignancy in patients with AL amyloidosis treated with lenalidomide

(Source: American Journal of Hematology)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Lenalidomide at Therapeutic and Supra‚?źtherapeutic Doses Does Not Prolong QTc Intervals in the Thorough QTc Study Conducted in Healthy Men

In conclusion, single doses of lenalidomide up to 50 mg were not associated with prolonged QTc intervals in healthy males. The C‚??QTc analysis further assured that lenalidomide doses up to 50 mg are not expected to prolong QTc intervals in patients. This article is protected by copyright. All rights reserved. (Source: Basic and Clinical Pharmacology and Toxicology)

Novel Agents Now Prevalent Method of Care for Multiple Myeloma

A majority of patients with multiple myeloma are being treated with novel agents such as thalidomide, bortezomib, and lenalidomide within a year of diagnosis instead of the chemotherapeutic regimens that were more prevalent a decade ago, according to a new study. (Source: Cancer Network)

Secondary Cancer Risk Found With Multiple Myeloma Maintenance Therapies

Multiple myeloma patients are at increased risk of developing myelodysplastic syndrome or acute leukemia after maintenance lenalidomide or thalidomide treatment, according to a new study. (Source: Cancer Network)

Myeloma and MGUS

Abstract: Plasma cell disorders result from a clonal proliferation of bone marrow plasma cells and range from the relatively benign monoclonal gammopathy of undetermined significance (MGUS) to malignant myeloma. A serum or urine monoclonal protein is usually detectable. MGUS is asymptomatic but can progress to myeloma or lymphoma. Myeloma is generally a disease of the elderly and presents with variable problems that include anaemia, bone pain and fractures, spinal cord compression, renal failure, hypercalcaemia, recurrent infections and hyperviscosity. Diagnosis is based on examination of the bone marrow, with prognosis influenced by specific genetic abnormalities. Treatment is required following the development of myeloma-related organ or tissue impairment. It is an incurable disease and ...

Myelodysplastic syndromes: What do hospitalists need to know?

Myelodysplastic syndromes (MDS) comprise a heterogeneous group of clonal hematopoietic stem cell disorders characterized by dysplasia, ineffective hematopoiesis leading to peripheral blood cytopenias, and a variable risk of leukemic progression. MDS primarily affects the elderly, and although its prevalence is increasing, MDS is frequently overlooked and underdiagnosed. MDS should be suspected in any patient with unexplained cytopenias, and a bone marrow evaluation is ultimately needed to make the diagnosis and exclude other causes of bone marrow failure. The last 15 years have witnessed significant advances in our understanding of the complex pathogenesis, classification and prognostication, and therapeutic approaches to MDS. Several prognostic models facilitate outcome prediction and ris...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Diagnosis and therapy of multiple myeloma.

Authors: Palumbo A, Cerrato C Abstract Many advances in the treatment of multiple myeloma have been made due to the use of transplantation and the introduction of novel agents including thalidomide, lenalidomide, and bortezomib. The first step is recognizing the symptoms and starting prompt treatment. Different strategies should be selected for young and elderly subjects. Young patients are commonly eligible for transplantation, which is now considered the standard approach for this setting, and various inductions therapies containing novel agents are available before transplantation. Elderly patients are usually not eligible for transplantation, and gentler approaches with new drugs combinations are used for their treatment. PMID: 23682217 [PubMed - in process] (Source: The Ko...

Lenalidomide in the treatment of plasma cell dyscrasia: state of the art and perspectives.

Authors: Palumbo A, Cavallo F PMID: 23633539 [PubMed - in process] (Source: Haematologica)

Paradoxical effect of lenalidomide on cytokine/growth factor profiles in multiple myeloma

Paradoxical effect of lenalidomide on cytokine&#47;growth factor profiles in multiple myeloma British Journal of Cancer advance online publication, April 30 2013. doi:10.1038/bjc.2013.186 Authors: S Ma&#239;ga, P Gomez-Bougie, S Bonnaud, C Gratas, P Moreau, S Le Gouill, C Pellat-Deceunynck & M Amiot (Source: British Journal of Cancer AOP)

Management of older adults with multiple myeloma

Abstract: Two-thirds of patients with multiple myeloma are aged 65years or more and the prevalence of multiple myeloma in elderly patients is expected to rise in the next future. Patients older than 65years are usually considered ineligible for transplantation. The introduction of novel agents, such as the immunomodulatory drugs thalidomide and lenalidomide and the proteasome inhibitor bortezomib, combined with conventional chemotherapy, has radically changed the treatment paradigm of elderly patients and improved outcome. A sequential approach, consisting of an induction regimen associated with a high rate of complete response, followed by consolidation/maintenance therapy, induces a profound cytoreduction and delays relapse, thus improving survival. Novel agents associated with reduced-i...

Efficacy and Safety of Busulfan-Based Conditioning Regimens for Multiple Myeloma.

Authors: Reece D, Song K, Leblanc R, Mezzi K, Olujohungbe A, White D, Zaman F, Belch A Abstract Multiple myeloma is a malignancy of B cells characterized by accumulation of abnormal plasma cells in the bone marrow. In the past 20 years, the use of high-dose therapies and novel agents has resulted in significant and meaningful improvements in survival. Autologous stem cell transplantation (auto-SCT) following a high-dose melphalan-conditioning regimen represents the standard of care for younger patients as well as older patients with a good performance status. A number of strategies have been proposed to improve the outcome of auto-SCTs, including the incorporation of new agents such as thalidomide, lenalidomide, and bortezomib into the induction regimen administered before auto-SCT...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

A G polymorphism in the CRBN gene acts as a biomarker of response to treatment with lenalidomide in low/int-1 risk MDS without del(5q)

A G polymorphism in the CRBN gene acts as a biomarker of response to treatment with lenalidomide in low&#47;int-1 risk MDS without del(5q) Leukemia advance online publication, April 26 2013. doi:10.1038/leu.2013.59 Authors: V Sardnal, A Rouquette, S Kaltenbach, C Bally, V Chesnais, C Leschi, L Ades, V Santini, S Park, A Toma, P Fenaux, F Dreyfus, M Fontenay & O Kosmider (Source: Leukemia)

Oral lenalidomide with rituximab in relapsed or refractory diffuse large cell, follicular and transformed lymphoma: a phase II clinical trial

Authors: M Wang, N Fowler, N Wagner-Bartak, L Feng, J Romaguera, S S Neelapu, F Hagemeister, M Fanale, Y Oki, B Pro, J Shah, S Thomas, A Younes, C Hosing, L Zhang, K J Newberry, M Desai, N Cheng, M Badillo, M Bejarano, Y Chen, K H Young, R Champlin, L Kwak & L Fayad (Source: Leukemia)

Response to lenalidomide in myelodysplastic syndromes with del(5q): influence of cytogenetics and mutations

This study reveals the importance of a low baseline platelet count, karyotypic complexity and TP53 mutational status for response to lenalidomide treatment. It supports the molecular study of TP53 in MDS patients treated with lenalidomide. (Source: British Journal of Haematology)

Low RPS14 expression in MDS without 5q ‚?ź aberration confers higher apoptosis rate of nucleated erythrocytes and predicts prolonged survival and possible response to lenalidomide in lower risk non‚?ź5q‚?ź patients

ConclusionLower RPS14 expression in MDS patients without 5q deletion is associated with increased apoptosis of nucleated erythrocytes in lower risk MDS. Additionally, lower RPS14 predicts prolonged survival and possible response to lenalidomide in lower risk MDS patients. (Source: European Journal of Haematology)

Association of Th1 and Th2 cytokines with transient inflammatory reaction during lenalidomide plus dexamethasone therapy in multiple myeloma.

Authors: Harada T, Ozaki S, Oda A, Fujii S, Nakamura S, Miki H, Kagawa K, Takeuchi K, Matsumoto T, Abe M Abstract Transient inflammatory reactions have been reported in a subpopulation of patients with multiple myeloma (MM) during lenalidomide (Len) plus dexamethasone (DEX) therapy. Here, we examined serum levels of Th1 (IL-2 and IFN-ő≥) and Th2 cytokines (IL-6 and TNF-őĪ) in nine refractory or relapsed MM patients treated with Len plus low-dose DEX. Six patients showed elevation of C-reactive protein (CRP) after the initiation of therapy. In these patients, IFN-ő≥ and IL-6 were also elevated in two and three patients, respectively. The remaining three patients showed no appreciable changes in CRP or these cytokines. Furthermore, Len enhanced the production of both Th1 and Th2 cyto...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Immunoglobulin light chain amyloidosis: 2013 update on diagnosis, prognosis, and treatment

Disease OverviewImmunoglobulin (Ig) light chain amyloidosis is a clonal, nonproliferative plasma cell disorder in which fragments of Ig light chain are deposited in tissues. Clinical features depend on organs involved but can include restrictive cardiomyopathy, nephrotic syndrome, hepatic failure, peripheral/autonomic neuropathy, and atypical multiple myeloma. DiagnosisTissue biopsy stained with Congo red demonstrating amyloid deposits with apple‚?źgreen birefringence is required for diagnosis. Invasive organ biopsy is not required because amyloid deposits can be found in bone marrow biopsy or subcutaneous fat aspirate in 85% of patients. Verification that amyloid is of immunoglobulin origin is mandatory. PrognosisN‚?źterminal pro‚??brain natriuretic peptide (NT‚?źproBNP), serum troponin T...

Cerebrospinal fluid penetrance of lenalidomide in meningeal myeloma

(Source: British Journal of Haematology)

Monoclonal antibodies: potential new therapeutic treatment against multiple myeloma

Abstract Despite recent treatments, such as bortezomib, thalidomide, and lenalidomide, therapy of multiple myeloma (MM) is limited, and MM remains an incurable disease associated with high mortality. The outcome of patients treated with cytotoxic therapy has not been satisfactory. Therefore, new therapies are needed for relapsed MM. A new anticancer strategy is the use of monoclonal antibodies (MoAbs) that represent the best available combination of tumor cytotoxicity, environmental signal privation, and immune system redirection. Clinical results in patients with relapsed/refractory MM suggest that MoAbs are likely to operate synergistically with traditional therapies (dexamethasone), immune modulators (thalidomide, lenalidomide), and other novel therapies (bortezomib); in addition, MoAbs...

Comparable efficacy and lower cost of PBSC mobilization with intermediate-dose cyclophosphamide and G-CSF compared with plerixafor and G-CSF in patients with multiple myeloma treated with novel therapies

Authors: F Awan, S T Kochuparambil, D E Falconer, A Cumpston, S Leadmon, K Watkins, D DeRemer, A Jillella, M Craig & M Hamadani (Source: Bone Marrow Transplantation)

Tumor-promoting immune-suppressive myeloid-derived suppressor cells in the multiple myeloma microenvironment in humans

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous, immature myeloid cell population with the ability to suppress immune responses. MDSCs have been characterized in infections, inflammatory diseases, and solid tumors; however, their presence and role in the tumor-promoting, immune-suppressive microenvironment in hematologic malignancies remains unclear. We assessed the presence, frequency, and functional characteristics of MDSCs in patients with newly diagnosed, relapsed, and relapsed/refractory multiple myeloma (MM) compared with healthy donors. Additionally, we evaluated the immunomodulatory effects of lenalidomide and bortezomib on MDSCs in MM. CD11b+CD14-HLA-DR-/lowCD33+CD15+ MDSCs were significantly increased in both the peripheral blood and the bone marrow of patients with ...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Autologous retransplantation for patients with recurrent multiple myeloma

CONCLUSIONSSalvage ASCT is capable of achieving sustained disease control in patients with multiple myeloma. The use of lenalidomide and bortezomib for reinduction has improved the results after salvage ASCT, suggesting that novel agents and salvage ASCT are complementary rather than alternative treatment approaches. Cancer 2013;000:000‚?ź000. ¬© 2013 American Cancer Society. (Source: Cancer)

High expression of cereblon (CRBN) is associated with improved clinical response in patients with multiple myeloma treated with lenalidomide and dexamethasone

Summary Cereblon (CRBN) has recently been identified as a target for immunomodulatory drugs (IMiDs) and its downregulation has been linked to resistance to lenalidomide. Here, we studied CRBN expression by real time polymerase chain reaction in 49 bone marrow samples of newly diagnosed patients with multiple myeloma treated with lenalidomide and dexamethasone. Median CRBN expression was 3¬∑45 in patients who achieved complete response, and 3¬∑75, 2¬∑01, 0¬∑78, and 0¬∑70 in those with very good partial response, partial response, stable disease and progressive disease respectively. CRBN expression levels correlated significantly with response to lenalidomide treatment (r¬†=¬†0¬∑48; P¬†&lt;¬†0¬∑001). Among established prognostic parameters, only beta‚?ź2‚?źmicroglobulin correlated with cereb...

Chronic lymphocytic leukemia cells induce defective LFA-1-directed T-cell motility by altering Rho GTPase signaling that is reversible with lenalidomide

T lymphocytes have an essential role in adaptive immunity and rely on the activation of integrin lymphocyte function&ndash;associated antigen-1 (LFA-1) to mediate cell arrest and migration. In cancer, malignant cells modify the immune microenvironment to block effective host antitumor responses. We show for the first time that CD4 and CD8 T cells from patients with chronic lymphocytic leukemia (CLL) exhibit globally impaired LFA-1&ndash;mediated migration and that this defect is mediated by direct tumor cell contact. We show that following the coculture of previously healthy T cells with CLL cells, subsequent LFA-1 engagement leads to altered Rho GTPase activation signaling by downregulating RhoA and Rac1, while upregulating Cdc42. Of clinical relevance, repair of this T-cell defect was de...

Haematological cancer: Lenalidomide improves response

Nature Reviews Clinical Oncology 10, 249 (2013). doi:10.1038/nrclinonc.2013.52 Author: Bryony Jones Lenalidomide consolidation can repair T-cell synapse signalling in patients with chronic lymphocytic leukaemia (CLL) and improve response in those treated with immunotherapy, according to a phase II consolidation trial published in Blood. &#8220;There was both a clinical and an immunological rationale for this study,&#8221; (Source: Nature Clinical Practice Oncology)

Successful salvage therapy using lenalidomide in a patient with relapsed multiple myeloma after allogeneic hematopoietic stem cell transplantation.

Authors: Suzuki T, Kusumoto S, Yoshida T, Mori F, Ito A, Ri M, Ishida T, Komatsu H, Niimi A, Iida S PMID: 23456263 [PubMed - in process] (Source: International Journal of Hematology)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Experience with lenalidomide in an Austrian non-study population with advanced myelofibrosis.

Authors: Burgstaller S, Fridrik M, Hojas S, K√ľhr T, Ludwig H, Mayrb√§url B, P√∂hnl R, P√∂tscher M, Schl√∂gl E, Zauner D, Thaler J, Gisslinger H Abstract Current literature provides conflicting evidence regarding the efficacy of lenalidomide in patients with myelofibrosis (MF). The aim of this work was to evaluate the efficacy of lenalidomide in patients with MF treated within a named patient program in Austria. A total of 22 patients with MF were treated with lenalidomide in 7 different centres throughout Austria. Median age of patients was 68 years. Primary MF was present in 13 patients. Eight patients had post-polycythemia vera (post-PV) and 1 post-essential thrombocythemia (post-ET) MF. According to the Dynamic International Prognostic Scoring System (DIPSS), all patients were ...

Carfilzomib: a next-generation proteasome inhibitor for multiple myeloma treatment.

Authors: Bilotti E Abstract Although the incidence of multiple myeloma (MM) is increasing, the median overall survival and the number of agents in the pipeline for treating MM also are increasing. Response rates higher than 80% are not uncommon in the frontline setting when the novel agents thalidomide, lenalidomide, and bortezomib are used in combination. Response rates and survival also have improved in disease that has relapsed after treatment with conventional therapies. The focus of research has now shifted to improving survival and disease response in patients refractory to current treatment paradigms. New agents are targeting new pathways, as well as existing mechanisms known to be effective, but with different safety profiles. Carfilzomib is a potent, selective, irreversibl...

Lenalidomide reduces survival of chronic lymphocytic leukemia cells in primary cocultures by altering the myeloid microenvironment

Chronic lymphocytic leukemia (CLL) cells depend on microenvironmental stimuli for their survival, provided for example by monocyte-derived nurse-like cells (NLCs). The immunomodulatory drug lenalidomide shows therapeutic effects in subgroups of CLL patients, and is believed to act via the microenvironment. To investigate the effects of lenalidomide on the survival support of NLCs, cocultures of monocytes and CLL cells were treated for 14 days with lenalidomide, which resulted in significantly decreased viability of CLL cells. Among the changes induced by this drug, we observed reduced expression of HLA-DR in NLCs as well as increased secretion of interleukin-10 (IL-10), indicating an altered inflammatory milieu in the cocultures. The increase in IL-10 levels lead to an induction of STAT1 p...

Lenalidomide in patients with chemotherapy‚?źinduced polyneuropathy and relapsed or refractory multiple myeloma: results from a single‚?źcentre prospective study

Abstract Lenalidomide, an immunomodulatory drug used in myeloma therapy, has been claimed to be less neurotoxic than thalidomide, but evidence is still weak. We prospectively assessed lenalidomide safety in myeloma patients to evaluate whether it would induce or modify a previously ensued chemotherapy‚?źinduced peripheral neuropathy (CIPN). Thirty consecutive patients (17 men, mean age 63.7‚??¬Ī‚??9.4) previously treated with bortezomib and/or thalidomide and starting on lenalidomide (25‚??mg/day for 21‚?źday cycles) for relapsed or refractory myeloma were assessed at baseline, 6, and 12‚??months from the beginning of lenalidomide with Total Neuropathy Score clinical version (TNSc), Eastern Cooperative Oncology Group (ECOG) performance status, and numeric rating scale (NRS) for pain. TNSc ...

Low RPS14 expression in MDS without 5q‚?ź aberration confers higher apoptosis rate of nucleated erythrocytes and predicts prolonged survival and possible response to lenalidomide in lower‚?źrisk non‚?ź5q‚?ź patients

ConclusionLower RPS14 expression in MDS patients without 5q deletion is associated with increased apoptosis of nucleated erythrocytes in lower‚?źrisk MDS. Additionally, lower RPS14 predicts prolonged survival and possible response to lenalidomide in lower‚?źrisk MDS patients.¬© 2013 John Wiley & Sons A/S (Source: European Journal of Haematology)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Sargramostim (GM-CSF) and lenalidomide in castration-resistant prostate cancer (CRPC): Results from a phase I-II clinical trial

Conclusions: Administration of GM-CSF and lenalidomide in patients with CRPC is safe with modest evidence of antitumor activity and no immune changes observed. (Source: Urologic Oncology: Seminars and Original Investigations)

Sargramostim (GM-CSF) and lenalidomide in castration-resistant prostate cancer (CRPC): Results from a phase I-II clinical trial(‚??‚??‚??)

CONCLUSIONS: Administration of GM-CSF and lenalidomide in patients with CRPC is safe with modest evidence of antitumor activity and no immune changes observed. PMID: 23510862 [PubMed - as supplied by publisher] (Source: Urologic Oncology)

Lenalidomide in combination with an activin A-neutralizing antibody: preclinical rationale for a novel anti-myeloma strategy

Authors: T Scullen, L Santo, S Vallet, M Fulciniti, H Eda, D Cirstea, K Patel, N Nemani, A Yee, A Mahindra & N Raje (Source: Leukemia)

Long‚?źterm efficacy of the combination of lenalidomide and rituximab in elderly relapsed/refractory diffuse large B‚?źcell lymphoma patients

(Source: Hematological Oncology)

Current approaches for the treatment of multiple myeloma.

Authors: Watanabe R, Tokuhira M, Kizaki M Abstract The development of novel therapeutic agents over the past decade, including the proteasome inhibitor, bortezomib, and the immunomodulatory drugs, lenalidomide and thalidomide, has resulted in improved outcomes for patients with multiple myeloma. However, there is still considerable controversy as to which regimen should be used as first-line therapy, which patients should be considered for autologous or allogeneic transplantation, and how consolidation or maintenance therapy is used in patients that have a good response to first-line therapy. The present paper will review clinical evidence from previous and ongoing studies to explore issues related to these questions. PMID: 23475758 [PubMed - in process] (Source: International ...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Biology and treatment of HTLV-1 associated T-cell lymphomas

Adult T-cell leukemia-lymphoma (ATL) is a distinct peripheral T-lymphocytic malignancy associated with human T-cell lymphotropic virus type I (HTLV-1) endemics in several regions of the world including the south-west Japan. The three major routes of HTLV-1 transmission are mother-to-child infections via breast milk, sexual intercourse, and blood transfusions. A HTLV-1 infection early in life, presumably from breast feeding, is crucial to the development of ATL. The estimated cumulative risk of developing ATL among HTLV-1-positive individuals is about 3% after transmission from the mother. The diversity in clinical features and prognosis of patients with this disease has led to its subtype-classification into acute, lymphoma, chronic, and smoldering types defined by organ involvement, lacta...

[Effectiveness and safety of lenalidomide in myelofibrosis patients: a case series from the Spanish compassionate use program.]

Conclusions: Continuous treatment with lenalidomide is active in MF patients pretreated heavily. Lenalidomide-induced myelosuppression and other associated toxicities are manageable with dose adjustments. PMID: 23789757 [PubMed - as supplied by publisher] (Source: Farmacia Hospitalaria)

Multiple myeloma: 2013 update on diagnosis, risk‚?źstratification, and management

Sequential combination of azacitidine and lenalidomide in del(5q) higher-risk myelodysplastic syndromes or acute myeloid leukemia: a phase I study

Authors: U Platzbecker, F Braulke, A K&#252;ndgen, K G&#246;tze, G Bug, C Sch&#246;nefeldt, K Shirneshan, C R&#246;llig, M Bornh&#228;user, R Naumann, J Neesen, A Giagounidis, W-K Hofmann, G Ehninger, U Germing, D Haase & M Wermke (Source: Leukemia)

Heparan sulfate proteoglycans in the control of B cell development and the pathogenesis of multiple myeloma

Abstract Heparan sulfate proteoglycans (HSPGs) have essential functions during embryonic development and throughout postnatal life. To exert these functions, they undergo a series of processing reactions by heparan sulfate modifying enzymes (HSMEs), which endows them with highly modified HS domains that provide specific docking sites for a large number of bio‚?źactive molecules. The development and antigen‚?źdependent differentiation of normal B lymphocytes, as well as the growth and progression of B‚?źlineage malignancies, are orchestrated by an array of growth factors, cytokines, and chemokines many of which display HS binding. As discussed in this review, tightly regulated HSPG expression is a requirement for normal B cell maturation, differentiation and function. In addition, the HSPG ...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

LCNDG Rapid Review: Lenalidomide for 1st relapse multiple myeloma after bortezomib

Source: London Cancer New Drugs Group Area: Evidence &#62; Drug Specific Reviews NICE recommends the use of lenalidomide for relapsed multiple myeloma only in those who have received two or more prior therapies. &#160; The best available evidence to support the use of lenalidomide and dexamethasone for the treatment of relapsed or refractory multiple myeloma comes from two phase III studies (MM-009 and MM-010). Both trials compared lenalidomide/dexamethasone to dexamethasone alone, and both trials used a primary endpoint of time to disease progression. There was only a limited number of patients in the two phase III studies who match the criteria for this application for funding, i.e. following one prior line of therapy- bortezomib. The time to progression was significantly longer for...

FDA Approves Pomalidomide for Advanced Multiple Myeloma

Pomalidomide has been approved for the treatment of patients with multiple myeloma whose disease has progressed after treatment with at least two prior therapies, including lenalidomide and bortezomib,... (Source: OncologySTAT Latest News)

Horizon scanning: Lenalidomide on fast-track review by the USFDA for mantle cell lymphoma

Source: Reuters Health News Area: News According to a report by Reuters Health News, the US Food and Drug Administration (FDA) has granted priority review for lenalidomide used for the treatment of relapsed or refractory mantle cell lymphoma (Source: NeLM - News)

Celgene wins Chinese regulatory OK for Revlimid

(Reuters) - Celgene Corp on Monday said its drug Revlimid won full regulatory approval in China for patients with relapsed or refractory multiple myeloma, a type of cancer that starts in the plasma cells in the bone marrow. (Source: Reuters: Health)

Pomalyst (pomalidomide) For Advanced Multiple Myeloma Approved By FDA

Pomalyst (pomalidomide) has been approved by the FDA for the treatment of patients with multiple myeloma whose cancer progressed after being treated with other medications. Pomalyst, which is presented in capsule form, modulates the immune system so that the patient's own body destroys cancerous cells and undermines their growth. Pomalidomide is aimed at multiple myeloma patients who had been administered at least two previous therapies which did not stop the progression of the disease within two months (relapsed and refractory), including therapies with bortezomib and lenalidomide... (Source: Health News from Medical News Today)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Horizon scanning: US FDA approves pomalidomide (Pomalyst¬ģ) for advanced multiple myeloma

The objective response rate was 7.4% in the monotherapy arm (median duration of response not yet reached) and 29.2% in the combination group (median duration of response of 7.4 months). &#160; Pomalidomide carries a Boxed Warning alerting patients and healthcare professionals that it should not be used in pregnant women due to a risk of severe life-threatening birth defects, and that it can cause blood clots. It is available only through a Risk Evaluation and Mitigation Strategy (REMS) Program, similar to those in ... (Source: NeLM - News)

Long‚?źterm outcome after allogeneic stem‚?źcell transplantation with reduced‚?źintensity conditioning in patients with multiple myeloma

In conclusion, we observe that long‚?źterm disease control can be expected in a subset of MM patients undergoing RIC Allo‚?źSCT. After 10 years the OS and PFS were 32% and 24%, respectively. The PFS curve after Allo‚?źSCT stabilizes in time with a plateau after 6 years post Allo‚?źSCT. (Source: American Journal of Hematology)

Phase II Study of Lenalidomide and Rituximab As Salvage Therapy for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia [Hematologic Malignancies]

Conclusion The combination of lenalidomide and rituximab is active in patients with recurrent CLL and warrants further investigation. (Source: Journal of Clinical Oncology)

Improving overall survival and overcoming adverse prognosis in the treatment of cytogenetically high-risk multiple myeloma

Multiple myeloma (MM) is a heterogeneous disease with certain genetic features [eg, t(4;14), del17p] associated with worse outcome. The introduction of thalidomide, lenalidomide, and bortezomib has dramatically improved the outlook for patients with MM, but their relative benefit (or harm) for different genetic patient subgroups remains unclear. Unfortunately, the small number of patients in each subgroup frequently limits the analysis of high-risk patients enrolled in clinical trials. Strategies that result in survival of high-risk genetic subgroups approximating that of patients lacking high-risk features are said to overcome the poor prognostic impact of these high-risk features. This outcome has been difficult to achieve, and studies in this regard have so far been limited by inadequat...

Lenalidomide, rituximab combination shows promise in CLL

Badoux XC. J Clin Oncol. 2012;doi:10.1200/JCO.2012.42.8623. (Source: HemOncToday.com)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Chromosome 5q deletion is extremely rare in patients with myelofibrosis

Abstract: Chromosome 5q deletion can be found in rare cases of myelofibrosis (MF) but the incidence, clinical significance and response to therapies are not well studied. We retrospectively reviewed charts of 939 patients with MF and identified 8 patients [0.8%] who carried 5q deletion. Of the 8, seven had complex cytogenetic abnormalities and one had additional clone with different cytogenetic abnormality. All 8 had significant three-lineage pancytopenia. Three patients took lenalidomide and one (patient with 5q-clone) achieved long-lasting hematologic response. Two patients responded to JAK2 inhibitor therapy. MF patients with 5q deletion often have complex karyotype and poor outcome. (Source: Leukemia Research)

Lenalidomide does not increase AML progression risk in RBC transfusion-dependent patients with Low- or Intermediate-1-risk MDS with del(5q): a comparative analysis

Authors: A Kuendgen, M Lauseker, A F List, P Fenaux, A A Giagounidis, N A Brandenburg, J Backstrom, A Glasmacher, J Hasford & U Germing (Source: Leukemia)

Enhanced cross-priming of naive CD8+ T cells by DCs treated by the IMiDs(¬ģ) immunomodulatory compounds Lenalidomide and Pomalidomide.

Enhanced cross-priming of naive CD8+ T cells by DCs treated by the IMiDs(¬ģ) immunomodulatory compounds Lenalidomide and Pomalidomide. Immunology. 2013 Feb 1; Authors: Henry JY, Labarthe MC, Meyer B, Dasgupta P, Dalgleish AG, Galustian C Abstract The IMiDs(¬ģ) immunomodulatory compounds, lenalidomide and pomalidomide are agents with anti-inflammatory, immunomodulatory and anti-cancer activity. An excellent success rate has been shown for multiple myeloma in phase I / II clinical trials leading to FDA approval of lenalidomide. One mechanism by which these drugs could enhance anti-tumour immunity may be through enhanced dendritic cell (DC) function. Thalidomide, a compound structurally related to lenalidomide and pomalidomide is known to enhance DC function, and we have inves...

Peripheral neuropathy in multiple myeloma patients receiving lenalidomide, bortezomib, and dexamethasone (RVD) therapy

(Source: Blood)

The cost-effectiveness of initial treatment of multiple myeloma in the u.s. With bortezomib plus melphalan and prednisone versus thalidomide plus melphalan and prednisone or lenalidomide plus melphalan and prednisone with continuous lenalidomide maintenance treatment.

Authors: Garrison LP, Wang ST, Huang H, Ba-Mancini A, Shi H, Chen K, Korves C, Dhawan R, Cakana A, van de Velde H, Corzo D, Duh MS Abstract The outlook for transplant-ineligible multiple myeloma patients has improved enormously over recent years with the incorporation of new agents into standard regimens. Novel regimens combine melphalan and prednisone (MP) with bortezomib (VMP), with thalidomide (MPT), and with lenalidomide with (MPR-R) and without (MPR) lenalidomide maintenance. The efficacy, safety, and cost-effectiveness of these regimens have not yet been compared; therefore, we conducted a pharmacoeconomic analysis using data from randomized controlled trials versus MP. Using a Markov model developed from a U.S. payer's perspective, we compared VMP with MPT and MPR-R over a l...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Health care costs and resource utilization, including patient burden, associated with novel-agent-based treatment versus other therapies for multiple myeloma: findings using real-world claims data.

Conclusions. Adjusted analyses of real-world claims data show that total health care costs, as well as patient out-of-pocket costs, are higher with THAL/LEN treatment episodes than with BOR/OTHER therapies. Additionally, similar rates of ambulatory visits suggest that any perceived advantage in patient convenience of the orally administered drugs THAL/LEN is not supported by these data. PMID: 23299776 [PubMed - in process] (Source: The Oncologist)

Current Therapeutic Strategy for Multiple Myeloma

This is a review regarding the current therapeutic strategies in the management of multiple myeloma. Due to the introduction of several new effective therapeutic agents, multiple myeloma is one of the most active and changing fields in clinical oncology. Multiple myeloma is caused by the expansion of monoclonal plasma cells and secretion of M-protein (immunoglobulins, Bence Jones protein and free light chain). High-dose chemotherapy supported with autologous peripheral blood stem cells is an effective treatment for the disease. However, multiple myelomas are still difficult to cure and require long-term disease control. In recent years, the introduction of novel drugs (bortezomib, lenalidomide and thalidomide) has improved treatment. (Source: Japanese Journal of Clinical Oncology)

MHRA Drug Safety Update: routine monitoring of liver function for lenalidomide (RevlimidT)

Source: MHRA Area: Evidence &#62; Medication Safety The January issue of the MHRA's Drug Safety Update recommends the routine monitoring of hepatic function with lenalidomide (RevlimidT) following reports of suspected adverse hepatic reactions and evidence to suggest that lenalidomide may be associated with drug-induced liver injury. &#160; In light of this evidence, healthcare professionals are given the following advice: &#160; .&#160;Routine monitoring of liver function with the same frequency as haematological monitoring* is recommended for patients receiving lenalidomide. This is particularly important in patients with a history of, or concurrent, viral liver infection, or when lenalidomide is given at the same time as other medications known to be associated with liver injur...

Lenalidomide Branches Out to Lymphoma Therapy

ATLANTA (IMNG) - Lenalidomide, already an important agent in the treatment of multiple myeloma, is also flexing its muscles against non-Hodgkin's lymphomas, reported researchers in two clinical trials... (Source: OncologySTAT Latest News)

[News] 54th ASH Annual Meeting

Pomalidomide plus low-dose dexamethasone is an effective treatment for refractory multiple myeloma according to results of a phase 3 open-label randomised trial. Meletios Dimopoulos (Athens, Greece) and colleagues found patients refractory to bortezomib, thalidomide, or lenalidomide treated with pomalidomide plus dexamethasone had a significant improvement in progression-free survival (HR 0·45, p&lt;0·001) and overall survival (HR 0·53, p&lt;0·001) compared with patients treated with high-dose dexamethasone alone. (Source: The Lancet Oncology)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Survival Improved In Multiple Myeloma Relapse By New Drug

Researchers at Moffitt Cancer Center and colleagues have investigated the safety, efficacy and the maximum tolerated dose of pomalidomide for patients with multiple myeloma who have disease relapsed after treatments with other drugs, such as bortezomib and lenalidomide. This phase I clinical trial enrolled 38 patients, and pomalidomide provided a minimal or better response for 42 percent of the patients, a partial response or better for 21 percent, and a complete response for 3 percent... (Source: Health News from Medical News Today)

Lenalidomide in combination with gemcitabine as first-line treatment for patients with metastatic carcinoma of the pancreas: A Sarah Cannon Research Institute phase II trial.

Conclusions: The observed 6-month OS (37%) of lenalidomide with gemcitabine does not suggest improvement compared with historical results with gemcitabine alone. Toxicities and dose modifications likely limited dose intensity. Further development of this regimen in pancreas cancer is not recommended. PMID: 23358470 [PubMed - as supplied by publisher] (Source: Cancer Biology and Therapy)

Lenalidomide: First report of cold autoimmune haemolytic anaemia: case report

(Source: Reactions)

New drug improves survival in multiple myeloma relapse, Moffitt Cancer Center researchers say

(H. Lee Moffitt Cancer Center & Research Institute) Researchers at Moffitt Cancer Center and colleagues have investigated the safety, efficacy and the maximum tolerated dose of pomalidomide for patients with multiple myeloma who have disease relapsed after treatments with other drugs, such as bortezomib and lenalidomide. This phase I clinical trial enrolled 38 patients, and pomalidomide provided a minimal or better response for 42 percent of the patients, a partial response or better for 21 percent, and a complete response for 3 percent. (Source: EurekAlert! - Medicine and Health)

High cereblon expression is associated with better survival in patients with newly diagnosed multiple myeloma treated with thalidomide maintenance

Recently, cereblon (CRBN) expression was found to be essential for the activity of thalidomide and lenalidomide. In the present study, we investigated whether the clinical efficacy of thalidomide in multiple myeloma is associated with CRBN expression in myeloma cells. Patients with newly diagnosed multiple myeloma were included in the HOVON-65/GMMG-HD4 trial, in which postintensification treatment in 1 arm consisted of daily thalidomide (50 mg) for 2 years. Gene-expression profiling, determined at the start of the trial, was available for 96 patients who started thalidomide maintenance. In this patient set, increase of CRBN gene expression was significantly associated with longerprogression-free survival (P = .005). In contrast, no association between CRBN expression and survival was obser...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Efficacy of thalidomide‚?źbased therapy following lenalidomide plus dexamethasone in patients with relapsed/refractory multiple myeloma

(Source: American Journal of Hematology)

Factors impacting stem cell mobilization failure rate and efficiency in multiple myeloma in the era of novel therapies: experience at Memorial Sloan Kettering Cancer Center

Authors: M Pozotrigo, N Adel, H Landau, A Lesokhin, N Lendvai, D J Chung, D Chimento, E Riedel, X Chen, L Reich, R Comenzo, S Giralt & H Hassoun (Source: Bone Marrow Transplantation)

Efficacy of lenalidomide in POEMS syndrome: A retrospective study of 20 patients

We report the use of a combination of lenalidomide and dexamethasone in 20 patients with POEMS syndrome. Four patients were newly diagnosed, and 16 had relapsed or progressed after treatment. All but one of the patients responded: clinical improvements were noted in neuropathies (16/20) organomegaly (13/13), peripheral edema (14/15), and pulmonary hypertension (5/5). At least a very good partial response was noted in 68% of patients, with partial responses in 26%. Serum VEGF levels fell markedly in all 17 patients with available values. Twelve patients had 18‚?źFDG‚?źPET/CT at diagnosis (11 with positive findings), and nine patients during follow‚?źup. The number of lesions fell markedly in five cases and remained stable in two cases, while two patients became negative. During a median fol...

Clinical regressions and broad immune activation following combination therapy targeting human NKT cells in myeloma

Natural killer T (iNKT) cells can help mediate immune surveillance against tumors in mice. Prior studies targeting human iNKT cells were limited to therapy of advanced cancer and led to only modest activation of innate immunity. Clinical myeloma is preceded by an asymptomatic precursor phase. Lenalidomide was shown to mediate antigen-specific costimulation of human iNKT cells. We treated 6 patients with asymptomatic myeloma with 3 cycles of combination of &alpha;-galactosylceramide&ndash;loaded monocyte-derived dendritic cells and low-dose lenalidomide. Therapy was well tolerated and led to reduction in tumor-associated monoclonal immunoglobulin in 3 of 4 patients with measurable disease. Combination therapy led to activation-induced decline in measurable iNKT cells and activation of NK ce...

Development and validation of ultra-performance liquid chromatographic method with tandem mass spectrometry for the determination of lenalidomide in rabbit and human plasma

Conclusion: The proposed UPLC-MS/MS method is simple, rapid and highly sensitive, and hence it could be reliable for pharmacokinetic and toxicokinetic study in both animals and humans. (Source: Chemistry Central Journal)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Review of Revlimid highlights hepatotoxicity

(Source: Reactions)

Lenalidomide: Hyperbilirubinaemia: case report

(Source: Reactions)

Development and Validation of LC-MS/MS Method for the Quantitation of Lenalidomide in Human Plasma using Box-Behnken Experimental Design

, 2013, Accepted ManuscriptDOI: 10.1039/C2AN36701G, PaperM Saquib Hasnain, Shireen Rao, Mamoj Kumar Singh, Nitin Vig, Amit Gupta, Abdulla Ansari, Pradeep Sen, Pankaj Joshi, Shaukat ali AnsariFor the determination of lenalidomide (LENA) using Carbamazepine (Carba) as an internal standard (IS), an ultra-fast stability indicating LC-MS/MS method was developed, validated and optimized to support the clinical advancement....The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Analyst latest articles)

Light chain amyloidosis 2012: a new era

Summary AL amyloidosis patients with multi‚?źorgan and particularly cardiac involvement have historically been considered to have a bad prognosis. The introduction of autologous stem cell transplantation was associated with unacceptable toxicity in high‚?źrisk patients, but responding patients have prolonged overall survival. Toxicities can be decreased by careful patient selection, but this reduces the applicability of this treatment modality to a limited number of patients. Efforts are therefore needed to design novel more effective regimens, with the use of new medications, such as thalidomide, lenalidomide and bortezomib, next generation immunomodulatory drugs and proteasome inhibitors. Their combination with dexamethasone and alkylating agents show promising results, allowing a high p...

Inside this issue

See Salem et¬†al., pages 209‚??218, and Wolschke et¬†al., pages¬†134‚??142. Multiple myeloma (MM) is a rare but devastating plasma cell malignancy that affects mainly older adults. In the last ten years, induction regimens that combine the glucocorticoid-analog dexametasone (Dex) with novel chemotherapeutic agents, such as the proteasome-inhibitor bortezomib (BTZ) or the antiangiogenetic and immunomodulator drugs thalidomide and its derivative lenalidomide, have significantly increased the complete response (CR) rate before and after Allogenic Stem Cell Transplantation (ASCT) with a positive impact on progression-free survival. Maintenance therapy with thalidomide and lenalidomide may further prolong remission duration. However, in spite of these advances, MM remains incurable, as the dis...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Direct Healthcare Professional Communication: risk of hepatic disorders associated with lenalidomide (Revlimid¬ģ) use, in the context of other risk factors

Source: MHRA, Celgene Europe Limited Area: News Celgene, in agreement with the European Medicines Agency and the MHRA has issued important safety information following a recent review of hepatic disorders in its Pharmacovigilance database as of 26 December 2011, which noted an overall reporting rate of 0.67% for hepatic disorders in the patient population exposed to lenalidomide. &#160; The following information has been issued as a consequence: &#160; .&#160;In multiple myeloma patients treated with lenalidomide in combination with dexamethasone, some severe cases of liver injuries, including fatal cases, have been reported: acute hepatic failure, toxic hepatitis, cytolytic hepatitis, cholestatic hepatitis and mixed cytolytic/cholestatic hepatitis. &#160; .&#160;Lenalidomide ...

Lenalidomide-mediated enhanced translation of C/EBP{alpha}-p30 protein up-regulates expression of the antileukemic microRNA-181a in acute myeloid leukemia

Recently, we showed that increased miR-181a expression was associated with improved outcomes in cytogenetically normal acute myeloid leukemia (CN-AML). Interestingly, miR-181a expression was increased in CN-AML patients harboring CEBPA mutations, which are usually biallelic and associate with better prognosis. CEBPA encodes the C/EBP&alpha; transcription factor. We demonstrate here that the presence of N-terminal CEBPA mutations and miR-181a expression are linked. Indeed, the truncated C/EBP&alpha;-p30 isoform, which is produced from the N-terminal mutant CEBPA gene or from the differential translation of wild-type CEBPA mRNA and is commonly believed to have no transactivation activity, binds to the miR-181a-1 promoter and up-regulates the microRNA expression. Furthermore, we show that len...

Long‚?źterm molecular remission with lenalidomide treatment of relapsed chronic lymphocytic leukemia

We report the first case of long‚?źterm molecular remission with continuous lenalidomide treatment in a young patient with CLL relapsed to multiple treatments. Minimal residual disease was assessed by nested polymerase chain reaction on bone marrow samples with patient‚?źspecific primers. A 20‚?źyear‚?źold patient with standard‚?źrisk CLL was treated with lenalidomide after multiple relapses and achieved a four year long complete molecular response with minimal toxicities. Published biologic data support that lenalidomide induces an immune‚?źmediated control of CLL, and our case suggests that long‚?źterm treatment with lenalidomide is effective at a molecular level in patients with relapsed CLL. ¬© 2013 John Wiley & Sons A/S (Source: European Journal of Haematology)

Carfilzomib: a second-generation proteasome inhibitor for the treatment of relapsed and refractory multiple myeloma.

CONCLUSIONS: Carfilzomib is a safe and effective new treatment option for patients with relapsed MM refractory to bortezomib and thalidomide or lenalidomide. Randomized head-to-head trials with bortezomib will assist in formulary and treatment decisions in the context of PIs as a drug class. PMID: 23300152 [PubMed - in process] (Source: The Annals of Pharmacotherapy)

Health-related quality of life outcomes of lenalidomide in transfusion-dependent patients with Low- or Intermediate-1-risk myelodysplastic syndromes with a chromosome 5q deletion: Results from a randomized clinical trial

We report health-related quality of life (HRQL) outcomes assessed using the Functional Assessment of Cancer Therapy-Anemia (FACT-An) among 167 RBC transfusion-dependent patients with IPSS Low-/Intermediate-1-risk del5q31 MDS treated with lenalidomide versus placebo in a randomized phase 3 clinical trial, MDS-004. Mean baseline to 12 week changes in FACT-An Total scores improved following treatment with lenalidomide 5 and 10mg (+5.7 and +5.7, respectively) versus placebo (‚??2.8) (both p (Source: Leukemia Research)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Lenalidomide Holds Promise in Mantle Cell LymphomaLenalidomide Holds Promise in Mantle Cell Lymphoma

Among relapsed or refractory patients with mantle cell lymphoma, lenalidomide showed &quot;rapid and durable&quot; efficacy. Medscape Medical News (Source: Medscape Today Headlines)

Efficacy of Lenalidomide in POEMS Syndrome; A Retrospective Study of 20 Patients

Results of this study showed clinical improvement and low toxicity, with hematologic response and reduced VEGF levels, using a combination of lenalidomide and dexamethasone in the treatment of patients... (Source: OncologySTAT Journal Scans)

Development and Validation of LC-MS/MS Method for the Quantitation of Lenalidomide in Human Plasma using Box-Behnken Experimental Design

Analyst, 2012, Accepted ManuscriptDOI: 10.1039/C2AN36701G, PaperM Saquib Hasnain, Shireen Rao, Mamoj Kumar Singh, Nitin Vig, Amit Gupta, Abdulla Ansari, Pradeep Sen, Pankaj Joshi, Shaukat ali AnsariFor the determination of lenalidomide (LENA) using Carbamazepine (Carba) as an internal standard (IS), an ultra-fast stability indicating LC-MS/MS method was developed, validated and optimized to support the clinical advancement....The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Analyst latest articles)

Lenalidomide efficacy in activated B‚?źcell‚?źlike subtype diffuse large B‚?źcell lymphoma is dependent upon IRF4 and cereblon expression

Summary Durable responses with lenalidomide monotherapy have been reported in patients with non‚?źHodgkin lymphoma. In relapsed/refractory diffuse large B‚?źcell lymphoma (DLBCL), higher responses were observed in the activated B‚?źcell‚?źlike (ABC) subtype than in the germinal centre B‚?źcell‚?źlike subtype. Herein, the molecular mechanisms involved in the differential efficacy of lenalidomide in DLBCL subtypes were investigated. Using DLBCL cell lines, lenalidomide treatment was found to preferentially suppress proliferation of ABC‚?źDLBCL cells in vitro and delay tumour growth in a human tumour xenograft model, with minimal effect on non‚?źABC‚?źDLBCL cells. This tumouricidal effect was associated with downregulation of interferon regulatory factor 4 (IRF4), a hallmark of ABC‚?źDLBCL ce...

Bendamustine Plus Rituximab Followed by Maintenance Lenalidomide Increases PFS in Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Capsule Summary - Improved median PFS suggests that lenalidomide maintenance regimen contributes to improved response duration. (Source: Clinical Care Options Oncology - Leukemia)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Long-term Single-Agent Lenalidomide Well Tolerated in Previously Untreated CLL, With Improved Depth of Response Over Time

Capsule Summary - In this long-term follow-up of a phase II trial, it was shown that long-term single-agent lenalidomide was relatively well tolerated in patients with previously untreated CLL, although recurrence of tumor flare symptoms was noted upon resumption of lenalidomide in some patients even as late as cycle 28. (Source: Clinical Care Options Oncology - Leukemia)

Lenalidomide Plus Rituximab Active and Tolerable as Initial Therapy for Patients With Advanced Indolent NHL

Capsule Summary - High ORR, CR rates, and durable remissions with the combination; phase III trials in follicular lymphoma are under way. (Source: Clinical Care Options Oncology - Lymphoma)

Ofatumumab Plus Lenalidomide Active in Relapsed CLL

Capsule Summary - This phase II study evaluating the combination of the CD20-targeted antibody ofatumumab with lenalidomide showed the combination was safe and active in patients with relapsed CLL. (Source: Clinical Care Options Oncology - Leukemia)

Endothelial stress products and coagulation markers in patients with multiple myeloma treated with lenalidomide plus dexamethasone: an observational study

Summary In this prospective study of patients with relapsed or relapsed and refractory multiple myeloma (MM) treated with lenalidomide and dexamethasone, relationships between markers of endothelial stress and drug administration and incidence of venous thromboembolism (VTE) were assessed. Of 33 enrolled patients, laboratory and treatment data were available for 32 patients. Of these, 23 received pulsed dexamethasone (40¬†mg/day on days 1‚??4, 9‚??12 and 17‚??21 of each 28‚?źday cycle) and 9 received weekly dexamethasone (40¬†mg/day on days 1, 8, 15 and 21 of each cycle). The overall incidence of VTE was 9%. A decreasing trend in markers values was observed with intercellular adhesion molecule (P¬†=¬†0¬∑05), fibrinogen (P¬†=¬†0¬∑008), plasminogen activator inhibitor‚?ź1 (P¬†&lt;¬†0¬∑001), ...

Lenalidomide Well Tolerated and Active in Combination With Fludarabine and Rituximab for Previously Untreated CLL

Capsule Summary - In this phase I/II dose-finding study, 2 doses of lenalidomide were found to be effective and tolerable in combination with fludarabine and rituximab, providing a potential for use of lenalidomide as a substitute for cyclophosphamide in the FCR regimen. (Source: Clinical Care Options Oncology - Leukemia)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Phase 2 study of the lenalidomide and azacitidine combination in patients with higher-risk myelodysplastic syndromes

This study is registered at http://www.clinicaltrials.gov as NCT00352001. (Source: Blood)

ASH: Proteasome Inhibitor MLN9708 Shows Promise in Multiple Myeloma

Preliminary findings presented at ASH suggest a ‚??favorable emerging clinical profile‚?Ě for once weekly administration of MLN9708 in combination with lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma. (Source: Cancer Network)

Horizon scanning: Phase III data for pomalidomide in multiple myeloma

This study randomised 455 patients who had disease progression during treatment or within 60 days of completing their last myeloma therapy (median of 5 previous therapies) to receive pomalidomide (4mg days 1-21) plus low-dose dexamethasone (40mg days 1, 8, 15 and 22; n=302; arm A) or high-dose dexamethasone (40mg days 1-4, 9-12, and 17-20; n=153; arm B) every 28 days until disease progression or unacceptable toxicity. The primary endpoint was ... (Source: NeLM - News)

Lenalidomide Offers An Effective Alternative Treatment For Cutaneus Lupus Erythematosus

Although rare there are several treatments available for cutaneus lupus erythematosus (CLE). However other options are needed for people who do not respond to medication or relapse. A new study into the thalidomide derivative lenalidomide, published today in BioMed Central's open access journal Arthritis Research & Therapy, shows that treatment with lenalidomide is safe, with patients seeing an improvement in as little as two weeks... (Source: Health News from Medical News Today)

Efficacy of lenalidomide in POEMS syndrome; a retrospective study of 20 patients.

We report the use of a combination of lenalidomide and dexamethasone in 20 patients with POEMS syndrome. Four patients were newly diagnosed and 16 had relapsed or progressed after treatment. All but one of the patients responded: clinical improvements were noted in neuropathies (16/20) organomegaly (13/13), peripheral edema (14/15), and pulmonary hypertension (5/5). At least a very good partial response was noted in 68% of patients, with partial responses in 26%. Serum VEGF levels fell markedly in all 17 patients with available values. Twelve patients had 18‚?źFDG‚?źPET/CT at diagnosis (11 with positive findings), and 9 patients during follow‚?źup. The number of lesions fell markedly in 5 cases and remained stable in 2 cases, while 2 patients became negative. During a median follow‚?źup of...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Therapy refractory angioimmunoblastic T‚?źcell lymphoma in complete remission with lenalidomide

Angioimmunoblastic T‚?źcell lymphoma (AITL) is a rare clinicopathologic entity (1‚?ź2% of non‚?źHodgkin lymphoma), characterized by an aggressive course and dismal outcome with current therapies [1]. AITL typically presents with advanced stage disease, generalized lymphadenopathy, hepatosplenomegaly, polyclonal hypergammaglobulinemia and systemic symptoms. The systemic symptoms include: skin rash, often with pruritus, pleural effusion, arthritis and ascites. ¬© 2012 John Wiley & Sons A/S (Source: European Journal of Haematology)

International clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer

ConclusionsDissemination and implementation of good clinical practice for the management of VTE, the second cause of death in cancer patients, is a major public health priority.© 2012 International Society on Thrombosis and Haemostasis (Source: Journal of Thrombosis and Haemostasis)

Efficacy and safety of lenalidomide for refractory cutaneous lupus erythematosus

Lenalidomide, a thalidomide derivative, is effective and safe for the treatment of refractory cutaneous lupus erythematosus in patients recruited to a phase II clinical study. (Source: Arthritis Research and Therapy)

Lenalidomide-induced upregulation of CXCR4 in CD34+ hematopoietic cells, a potential mechanism of decreased hematopoietic progenitor mobilization

Lenalidomide-induced upregulation of CXCR4 in CD34&#43; hematopoietic cells, a potential mechanism of decreased hematopoietic progenitor mobilization Leukemia advance online publication, December 4 2012. doi:10.1038/leu.2012.323 Authors: S Li, J Fu, H Ma, M Y Mapara & S Lentzsch (Source: Leukemia)

Rhabdomyolysis in a multiple myeloma patient secondary to concurrent treatment with lenalidomide and pravastatin and to lenalidomide alone.

Authors: Shahan JL, Panu LD, Hildebrandt GC PMID: 23188472 [PubMed - in process] (Source: International Journal of Hematology)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

A randomized, double-blind, placebo-controlled phase 2 study evaluating the efficacy and safety of romiplostim treatment of patients with low or intermediate-1 risk myelodysplastic syndrome receiving lenalidomide

Conclusions: These data suggest that romiplostim administered to MDS patients during lenalidomide treatment may decrease the frequency of dose reductions/delays due to thrombocytopenia. Additional study is needed to confirm the results of this preliminary trial.Trial registrationClinicalTrials.gov NCT00418665. (Source: Journal of Hematology and Oncology)

Hodgkin‚??s lymphoma as a second cancer in multiple myeloma never exposed to lenalidomide

Content Type Journal ArticleCategory Letter to the EditorPages 1-3DOI 10.1007/s00277-012-1639-3Authors Chor Sang Chim, Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, SAR, ChinaPak Tat Choi, Department of Nuclear Medicine, Pamela Youde Nethersole Eastern Hospital, Hong Kong, SAR, ChinaWai Ki Lee, Department of Pathology, Pok Oi Hospital, Yuen Long, Hong Kong, SAR, China Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555 (Source: Annals of Hematology)

Immunomodulatory drugs lenalidomide and pomalidomide inhibit multiple myeloma-induced osteoclast formation and the RANKL/OPG ratio in the myeloma microenvironment targeting the expression of adhesion molecules

Multiple myeloma (MM)‚??induced osteoclast (OC) formation is mainly due to an imbalance of the receptor activator NF-őļB ligand (RANKL)‚??osteoprotegerin (OPG) ratio in favor of RANKL in the bone microenvironment and to the CCL3 production by MM cells. The purpose of the study was to investigate the effect of the immunomodulatory drugs on RANKL/OPG ratio, the production of pro-osteoclastogenic cytokines, and MM-induced OC formation. We found that in¬†vivo concentrations of both lenalidomide (LEN) and pomalidomide (POM) significantly blunted RANKL upregulation normalizing the RANKL/OPG ratio in human osteoprogenitor cells (PreOBs) when co-cultured with MM cells and also inhibited CCL3 production by MM cells. A reduction in CD49d expression, a molecule critically involved in RANKL upregulati...

Chronic myelomonocytic leukemia treatment with azacitidine: What have we learned so far?

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder classified as myelodysplastic/myeloproliferative neoplasm according to 2008 World Health Organization (WHO) classification. The disease is characterized by absolute monocytosis (>1√?106) in the peripheral blood persisting for at least three months. Diagnosis is based on morphologic (less than 20% of blasts in the peripheral blood and bone marrow, with dysplasia in one or more myeloid lineages) and cytogenetic abnormalities (in the absence of Philadelphia chromosome and PDGFR rearrangements) with careful exclusion of malignant conditions associated to monocytosis . The hypomethylating agent azacitidine was approved for treatment of International Prognostic Scoring System (IPSS) intermediate-2 and high-risk m...

Chronic Lymphocytic Leukemia With Deletion 17p: Emerging Treatment Options

One strategy would be to consider ‚??early treatment‚?Ě for patients with deletion 17p, with the goal being to delay disease progression. This strategy is currently being explored in several prospective clinical trials employing treatment regimens such as FCR, lenalidomide (Revlimid), alemtuzumab (Campath), ofatumumab (Arzerra), and others. (Source: Cancer Network)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Impressive activity of lenalidomide monotherapy in refractory angioimmunoblastic T‚?źcell lymphoma: report of a case with long‚?źterm follow‚?źup

Abstract Angioimmunoblastic T‚?źcell lymphoma (AITL) is characterized by an aggressive clinical course and unfavourable prognosis. Refractory AITL patients have very few treatment options. Lenalidomide has previously been reported to have clinical efficacy in this setting; however, long‚?źterm reports are limited. A 59‚?źyear‚?źold man was referred to the hospital with fatigue, skin rash, weight loss and generalized lymphadenopathy and was diagnosed with AITL; clinical stage was IV B with bone marrow involvement. The patient had an unsatisfactory response despite three lines of conventional chemotherapy and radiotherapy. The patient received lenalidomide monotherapy (25‚??mg once daily) on days‚??1 to 21 of every 28‚?źday cycle for six cycles, followed by maintenance therapy with six cycle...

Melphalan, lenalidomide and dexamethasone for the treatment of AL amyloidosis: results of a phase II trial.

In conclusion, this combination is associated with significant myelosuppression leading to dose modifications and producing minor hematologic responses in AL amyloidosis. http://clinicaltrials.gov/ct2/show/NCT00679367. PMID: 23144200 [PubMed - as supplied by publisher] (Source: Haematologica)

Lenalidomide as salvage treatment for multiple myeloma relapsing after allogeneic hematopoietic stem cell transplantation: a report from the SFGM-TC.

Conclusion. Lenalidomide can induce high response rates in myeloma relapsing after allogeneic stem cell transplantation at least in part by triggering an allogeneic anti-myeloma response. Induced graft-versus-host disease has to be put in balance with the potential benefit on disease control. Further immunologic studies would have an interest in understanding lenalidomide immunomodulatory activity in vivo. Key words: Allogeneic hematopoietic stem cell transplantation, graft versus host disease, IMiDs, Multiple Myeloma. PMID: 23144198 [PubMed - as supplied by publisher] (Source: Haematologica)

Current treatment strategies with lenalidomide in multiple myeloma and future perspectives

Future Oncology , October 2012, Vol. 8, No. 10, Pages 1223-1238. (Source: Future Oncology)

Long-term complete remission in a multiple myeloma patient after Stevens-Johnson syndrome due to lenalidomide therapy.

Authors: Musolino C, Alonci A, Catena S, Rizzotti P, Russo S, Rotondo F, Allegra A PMID: 23113590 [PubMed - as supplied by publisher] (Source: Acta Oncologica)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

[Desensitization to lenalidomide].

Authors: Ca√Īamares Orbis I, Garc√≠a Mu√Īoz C, Cortijo Cascajares S, M√©ndez Esteban ME PMID: 23461448 [PubMed - in process] (Source: Farmacia Hospitalaria)

Complete Remission of del(5q) Myelodysplastic Syndrome after 7 Days of Lenalidomide Therapy Gives an Alert!

Case Rep Oncol 2012;5:586‚??591 (DOI:10.1159/000345098) (Source: Karger Publishers)

Synthesis of hapten and preparation of specific polyclonal antibody with high affinity for lenalidomide, the potent drug for treatment of multiple myeloma

Conclusions: The high affinity of the antibody (IC50 = 10 ng/mL) will be useful in the development of an immunoassay system for the determination of plasma LND concentrations. Current research is going to optimize the assay conditions and validate the procedures for the routine application in clinical laboratories. (Source: Chemistry Central Journal)

Combined treatment with lenalidomide and epoetin alfa in lower-risk patients with myelodysplastic syndrome

This study is registered at www.clinicaltrials.gov as NCT00910858. (Source: Blood)

Abnormal serum free light chain ratio predicts poor overall survival in mantle cell lymphoma

This study was undertaken to investigate the prognostic impact of abnormal sFLC ratios in mantle cell lymphoma (MCL). two patient cohorts were analysed for sFLC parameters: a preliminary retrospective cohort and a uniformly treated cohort of 20 relapsed/refractory MCL patients, enrolled in a phase II clinical trial of single agent lenalidomide treatment. 52% of patients had an abnormality of one or more sFLC parameter (71% of the first cohort and 40% of the second cohort). In cohort two, a high baseline SFLC ratio correlated with poorer overall survival (OS) compared to a low/normal ratio (median OS: 1·4 months vs. 19 months respectively; P = 0·001). For patients presenting with an elevated sFLC ratio at trial entry a rise of &gt;35% in the sFLC ratio correlated with disease progress...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Dexamethasone/lenalidomide: Tetany, elevated alkaline phosphatase levels and osteosclerosis in an elderly patient: case report

(Source: Reactions)

Postallograft lenalidomide induces strong NK cell‚??mediated antimyeloma activity and risk for T cell‚??mediated GvHD: Results from a phase I/II dose-finding study

Lenalidomide may prevent relapses after allogeneic stem cell transplantation by promoting the immune-mediated graft-versus-tumor effect. We performed a prospective phase I/II study to define the dose-limiting toxicity and the immunologic effects of lenalidomide given early (day 100‚??180) after allograft for four cycles in patients with multiple myeloma. According to the Fibonacci design, 24 patients with a median age of 53 years were included. Dose-limiting toxicity was organ toxicity owing to graft-versus-host disease, and the maximum tolerable dose was 5¬†mg. The incidence of graft-versus-host disease after lenalidomide was 38%, occurring after a median of 22 days, and was beside organ toxicity, a leading cause to discontinue the study in 29% of the patients. Immune monitoring revealed ...

A highly sensitive Fluorimetric method for determination of lenalidomide in its bulk form and capsules via Derivatization with Fluorescamine

Conclusions: The proposed method is selective and involved simple procedures. In conclusion, the method is practical and valuable for routine application in quality control laboratories for determination of LND. (Source: Chemistry Central Journal)

Dexamethasone 3.3 mg/ml solution for injection - Revised SPC

Source: Hameln pharmaceuticals Ltd Area: Other Library Updates &#62; SPC Changes Section 4.5 of the dexamethasone 3.3mg/mL solution for injection SPC has been revised to include updated information about interactions with antiretrovirals and states: &#160; &#160; Antiretroviral protease inhibitors (ritonavir, darunavir, indinavir, lopinavir, &#160;saquinavir and efavirenz) are metabolised by CYP3A. Medicinal products that induce CYP3A activity, such as dexamethasone, may increase the clearance of medicines metabolised by CYP3A, resulting in lowered plasma concentrations. Certain antiretroviral protease inhibitors (ritonavir, indinavir) may also be inducers of CYP3A themselves and as a result may increase the plasma concentration of dexamethasone. &#160; &#160; S...

Second Primary Malignancies after Autologous Hematopoietic Cell Transplantation for Multiple Myeloma

Abstract: Recent studies demonstrate an increased risk of second primary malignancies (SPMs) in patients with multiple myeloma (MM) receiving maintenance lenalidomide after autologous stem cell transplantation (ASCT). We explored the possibility of other risk factors driving post-ASCT SPMs in patients with MM through analysis of our large transplantation database in conjunction with our Long-Term Follow-Up Program. We conducted a retrospective cohort study of 841 consecutive patients with MM who underwent ASCT at City of Hope between 1989 and 2009, as well as a nested case-control analysis evaluating the role of all therapeutic exposures before, during, and after ASCT. Median duration of follow-up for the entire cohort was 3.4 years (range, 0.3-19.9 years). Sixty cases with a total of 70 S...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

New Proteasome Inhibitors in Myeloma

Abstract&nbsp;&nbsp;Proteasome inhibition has a validated role in cancer therapy since the successful introduction of bortezomib for the treatment of multiple myeloma (MM) and mantle cell lymphoma, leading to the development of second-generation proteasome inhibitors (PI) for MM patients in whom currently approved therapies have failed. Five PIs have reached clinical evaluation, with the goals of improving efficacy and limiting toxicity, including peripheral neuropathy (PN). Carfilzomib, an epoxyketone with specific chymothrypsin-like activity, acts as an irreversible inhibitor and was recently FDA approved for the response benefit seen in relapsed and refractory MM patients previously treated with bortezomib, thalidomide and lenalidomide. ONX-0912 is now under evaluation as an oral ...

Lenalidomide worsens survival, adverse events in prostate cancer

A combination of lenalidomide plus docetaxel and prednisone treatment in patients with chemotherapy-naive prostate cancer leads to worse overall survival rates and increased toxicity compared with placebo, show study results. (Source: MedWire News - Oncology)

Lenalidomide Worsens Survival in Advanced Prostate Cancer

VIENNA (IMNG) - Lenalidomide failed to increase overall survival above what was achieved with docetaxel plus prednisone in a phase III trial, leading to doubts that it has any potential value in the treatment... (Source: OncologySTAT Latest News)

Lenalidomide‚??prednisone induction followed by lenalidomide‚??melphalan‚??prednisone consolidation and lenalidomide‚??prednisone maintenance in newly diagnosed elderly unfit myeloma patients

Lenalidomide&#8722;prednisone induction followed by lenalidomide&#8722;melphalan&#8722;prednisone consolidation and lenalidomide&#8722;prednisone maintenance in newly diagnosed elderly unfit myeloma patients Leukemia advance online publication, October 12 2012. doi:10.1038/leu.2012.271 Authors: P Falco, F Cavallo, A Larocca, D Rossi, T Guglielmelli, A Rocci, M Grasso, M L M Siez, L De Paoli, S Oliva, S Molica, R Mina, F Gay, G Benevolo, P Musto, P Omed&#232;, R Freilone, S Bringhen, A M Carella, G Gaidano, M Boccadoro & A Palumbo (Source: Leukemia)

Phase I study of lenalidomide and alemtuzumab in refractory chronic lymphocytic leukaemia: maintaining immune functions during therapy‚?źinduced immunosuppression

(Source: British Journal of Haematology)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma

Carfilzomib is a next-generation, selective proteasome inhibitor being evaluated for the treatment of relapsed and refractory multiple myeloma. In this open-label, single-arm phase 2 study (PX-171-003-A1), patients received single-agent carfilzomib 20 mg/m2 intravenously twice weekly for 3 of 4 weeks in cycle 1, then 27 mg/m2 for &le; 12 cycles. The primary endpoint was overall response rate (&ge; partial response). Secondary endpoints included clinical benefit response rate (&ge; minimal response), duration of response, progression-free survival, overall survival, and safety. A total of 266 patients were evaluable for safety, 257 for efficacy; 95% were refractory to their last therapy; 80% were refractory or intolerant to both bortezomib and lenalidomide. Patients had median of 5 prior li...

Revlimid Combo Fails as Prostate Cancer Therapy

VIENNA (MedPage Today) -- Adding lenalidomide (Revlimid) to other chemotherapy led to greater toxicity and worse survival in patients with untreated ÔĽŅcastration-resistant prostate cancer, results of a large trial showed. (Source: MedPage Today Primary Care)

Lenalidomide for del(5q) and Non-del(5q) Myelodysplastic Syndromes

This article will also discuss combination strategies with lenalidomide in higher risk disease. (Source: Seminars in Hematology)

Lenalidomide: Intrahepatic cholestasis: 2 case reports

(Source: Reactions)

Lenalidomide: Stevens-Johnson syndrome: case report

(Source: Reactions)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Stemness of B cell progenitors in multiple myeloma bone marrow.

Conclusions We propose that antigen-independent B cell differentiation stages are involved in disease origination and progression in myeloma. Further investigations of myeloma putative stem cell progenitors may lead to novel treatments to eradicate the potential reservoir of minimal residual disease. PMID: 22988056 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Circulating activin-A is elevated in patients with advanced multiple myeloma and correlates with extensive bone involvement and inferior survival; no alterations post-lenalidomide and dexamethasone therapy

Conclusions High circulating activin-A correlates with advanced features of myeloma, supporting the rationale for the use of activin-A antagonists, such as sotatercept in myeloma. The inability of RD to reduce activin-A reveals RD as a good candidate for combination therapies with activin-A antagonists in myeloma. (Source: Annals of Oncology)

How I treat plasma cell leukemia

Primary plasma cell leukemia (pPCL) is a rare and aggressive plasma cell proliferative disorder with a very poor prognosis and with distinct biologic, clinical, and laboratory features. Compared with multiple myeloma, pPCL presents more often with extramedullary involvement, anemia, thrombocytopenia, hypercalcemia, elevated serum &beta;2-microglobulin and lactate dehydrogenase levels, as well as impaired renal function. Many of the genetic aberrations observed in newly diagnosed pPCL are typically found in advanced multiple myeloma. These cytogenetic abnormalities and mutations lead to increased proliferation, enhanced inhibition of apoptosis, escape from immune surveillance, and independence from the BM microenvironment, with changes in expression of adhesion molecules or chemokine recept...

Emerging strategies for targeting cell adhesion in multiple myeloma.

Authors: Nair RR, Gebhard AW, Emmons MF, Hazlehurst LA Abstract Multiple myeloma (MM) is an incurable hematological cancer involving proliferation of abnormal plasma cells that infiltrate the bone marrow (BM) and secrete monoclonal antibodies. The disease is clinically characterized by bone lesions, anemia, hypercalcemia, and renal failure. MM is presently treated with conventional therapies like melphalan, doxorubicin, and prednisone; or novel therapies like thalidomide, lenalidomide, and bortezomib; or with procedures like autologous stem cell transplantation. Unfortunately, these therapies fail to eliminate the minimal residual disease that remains persistent within the confines of the BM of MM patients. Mounting evidence indicates that components of the BM-including extracellul...

Biological activity of lenalidomide in myelodysplastic syndromes with del5q: results of gene expression profiling from a multicenter phase II study

Abstract&nbsp;&nbsp;In vitro studies suggest that haploinsufficiency is involved in the pathogenesis of myelodysplastic syndromes (MDS). In patients with del5q cytogenetic abnormality, RPS-14 and microRNAs (miRNAs) play a major role. In a multicenter phase II single-arm trial with lenalidomide in anemic primary del5q MDS patients with low- or int-1 risk IPSS, biological changes from baseline were investigated. Gene expression profiling of selected genes was performed (TaqMan¬ģ Low Density Array Fluidic card, Applied Biosystems PRISM¬ģ 7900HT) and normalized against the expression of the 18S housekeeping gene from a pool of healthy subjects. Thirty-two patients were evaluated at baseline and after 3 and 6&nbsp;months of treatment. RPS-14, miR-145, and miR-146 were downregulated at bas...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

A phase II trial of cyclophosphamide, lenalidomide and dexamethasone in previously treated patients with AL amyloidosis.

Authors: Palladini G, Russo P, Milani P, Foli A, Lavatelli F, Nuvolone M, Perlini S, Merlini G Abstract Immune-modulatory drugs are active in immunoglobulin light-chain amyloidosis and the addition of alkylating agents can potentiate their action. In this phase II prospective trial we treated with cyclophosphamide, lenalidomide and dexamethasone 21 patients who were refractory (13, 62%) or relapsed (8, 38%) after prior treatment including melphalan in all cases, bortezomib in 4 and thalidomide in 6. The median number of cycles administered was 4 (range: 2-9 cycles). Severe adverse events were observed in 57% of patients, most common being neutropenia (29%). The hematologic response rate was 62%, with 1 complete response and 5 very good partial responses. Overall median survival was...

Thalidomide and its analogues in the treatment of Multiple Myeloma

Multiple myeloma is an incurable malignant disorder of mature B-cells that predominantly affects the elderly. The immunomodulatory drug (IMiD) thalidomide and its newer analogs demonstrate increased antitumor activity, and have had a positive impact on the natural history of multiple myeloma. Recent advances in the clinical application of these agents and in our understanding of their mechanism of action, and toxicity have made safer and smarter use of these drugs possible. This review discusses the available information regarding mechanisms of action, toxicity and clinical results on thalidomide, lenalidomide and pomalidomide in the therapy of multiple myeloma. (Source: BioMed Central)

New therapeutics for myelodysplastic syndromes

For what was once an orphan disease with no approved therapeutics, the last decade has brought renewed attention to a once ignored but relatively common hematologic malignancy. We now have three therapeutic agents that are approved by the Food and Drug Administration (FDA) for the treatment of patients with myelodysplastic syndromes (MDS) in the United States. Two of these, the azanucleosides, have activity across the prognostic and morphologic spectrum of the disease, acting as dual nucleoside cytotoxics and epigenetic modulators. Lenalidomide (Revlimid¬ģ) represents the first targeted therapeutic for myelodysplastic syndrome (MDS) that was approved by the FDA in 2005 for the treatment of red blood cell transfusion dependent patients with MDS and chromosome 5q deletion (del(5q)). Since th...

Single-dose pharmacokinetics of lenalidomide in healthy volunteers: dose proportionality, food effect, and racial sensitivity

Conclusion&nbsp;&nbsp;Lenalidomide displayed linear pharmacokinetics from doses 5‚??400&nbsp;mg in healthy subjects. Although food reduced bioavailability, this was not considered clinically relevant. Lenalidomide was generally well tolerated in both ethnic groups. Content Type Journal ArticleCategory Original ArticlePages 1-9DOI 10.1007/s00280-012-1966-zAuthors N. Chen, Department of Clinical Pharmacology, Translational Development, Celgene Corporation, Summit, NJ, USAC. Kasserra, Department of Clinical Pharmacology, Translational Development, Celgene Corporation, Summit, NJ, USAJ. Reyes, Department of Clinical Pharmacology, Translational Development, Celgene Corporation, Summit, NJ, USAL. Liu, Department of Clinical Pharmacology, Translational Development, Celgene Corporation...

Lenalidomide maintenance in myeloma

Authors: Alessandro Gozzetti, Marzia Defina & Monica Bocchia We strongly agree with Rajkumar (Haematological cancer: Lenalidomide maintenance&#8212;perils of a premature denouement. Haematological cancer (Source: Nature Clinical Practice Oncology)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Cancer drug lenalidomide may increase risk of second primary malignancies.

Authors: Aschenbrenner DS PMID: 22932050 [PubMed - in process] (Source: The American Journal of Nursing)

Lenalidomide maintenance after allogeneic HSCT seems to trigger acute graft-versus-host disease in patients with high-risk myelodysplastic syndromes or acute myeloid leukemia and del(5q): results of the LENAMAINT trial.

Authors: Sockel K, Bornhaeuser M, Mischak-Weissinger E, Trenschel R, Wermke M, Unzicker C, Kobbe G, Finke J, Germing U, Mohr B, Greiner J, Beelen D, Thiede C, Ehninger G, Platzbecker U, on behalf of the German MDS and Cooperative Transplant Study Group (GCTSG) PMID: 22952334 [PubMed - as supplied by publisher] (Source: Haematologica)

Thromboprophylaxis prescribing and thrombotic event rates in multiple myeloma patients treated with lenalidomide or thalidomide at a specialist cancer hospital

ConclusionBoth aspirin and enoxaparin thromboprophylaxis were prescribed for patients on both low‚?źrisk and high‚?źrisk immunomodulatory drug‚?źbased regimens, deviating from current consensus guidelines. Treatment of comorbidities constituted the rationale for maintenance on therapeutic warfarin. Fixed low‚?źdose warfarin was not prescribed. TE event rates (with any thromboprophylaxis) were consistent with those reported in the literature. Documentation of a chosen strategy was lacking for nearly a quarter of patients, resulting in uncertainty of treatment plan for other members of the multidisciplinary treating team. Centers need to work towards evidence‚?źbased institutional guidelines and improving documentation practices for thromboprophylaxis in their MM patients. (Source: Asia-Paci...

Phase 2 Study of the Lenalidomide and Azacitidine Combination in Patients With Higher-Risk Myelodysplastic Syndromes

Results of this multicenter phase II study in which 36 patients with high-risk myelodysplastic syndromes were enrolled to receive azacitidine and lenalidomide showed that the combination was well-tolerated... (Source: OncologySTAT Journal Scans)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Incidence of 17p deletions and TP53 mutation in myelodysplastic syndrome and acute myeloid leukemia with 5q deletion

Abstract TP53 mutations are frequent in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) with complex karyotype that include del(5q) and are often associated with deletion of 17p. They have also recently been observed in MDS with isolated del(5q). We assessed the incidence of 17p deletion detected by fluorescence in situ hybridization (FISH) and of TP53 mutations detected by direct sequencing and their correlation and prognostic value in 26 MDS and 17 AML with del(5q). In the 20 cases with isolated del(5q) or one additional abnormality, no 17p deletion was found and 3 of the 18 cases analyzed (17%) had TP53 mutation. In the 23 patients with complex karyotype, 17p deletion was suspected by conventional cytogenetics in 15 cases and confirmed by FISH in 10 of them, while TP53 m...

A phase 1/2 study of carfilzomib in combination with lenalidomide and low-dose dexamethasone as a frontline treatment for multiple myeloma

This study is registered at http://www.clinicaltrials.gov as NCT01029054. (Source: Blood)

Correlation of clinical response and response duration with miR-145 induction by lenalidomide in CD34+ cells from patients with del(5q) myelodysplastic syndrome.

We examined whether lenalidomide exposure upregulates miRNAs and mRNAs, previously shown to play a role in the disease phenotype of del(5q) myelodysplastic syndrome, in pretreatment CD34+ marrow cells. We hypothesized that increased expression would predict for clinical response. Changes in miR-143, miR-145, miR-146a, miR-146b, miR-378, miR-584, SPARC and RPS14 were examined in del(5q) (n = 10) and non-del(5q) (n = 18) myelodysplastic syndrome patient samples. Significantly increased expression of miR-143 (1.8-fold and 1.5-fold in del(5q) and non-del(5q), respectively), and miR-145 (1.9-fold and 1.6-fold in del(5q) and non-del(5q), respectively) was observed. In the del(5q) myelodysplastic syndrome cohort, transfusion independence correlated with a ‚?•1.3-fold increase in miR-145 expressio...

Evolving Chemotherapy Options for the Treatment of Myeloma Kidney: A 40-Year Perspective

Kidney impairment (KI) at the time of initial diagnosis is common in myeloma. The improvement of kidney function and the reversal of KI are of utmost importance. Recent advances have made it possible to reverse acute kidney damage due to myeloma in most patients, at least if treatment is immediately implemented. Immediate antimyeloma therapy and appropriate hydration are the most commonly used treatment modalities for the management of acute KI related to myeloma. Mechanical approaches can only temporarily reduce the free light-chain load, and without effective chemotherapy they are probably not able to significantly improve kidney function. However, the role of mechanical approaches together with effective chemotherapy is still being explored. Thalidomide, lenalidomide, and bortezomib hav...

Fifty Years of Melphalan Use in Hematopoietic Stem Cell Transplantation

Abstract: Melphalan remains the most widely used agent in preparative regimens for hematopoietic stem cell transplantation (SCT). From its initial discovery more than 50 years ago, it has been gradually incorporated in the conditioning regimens for both autologous and allogeneic transplantations because of its myeloablative properties and broad antitumor effects as a DNA alkylating agent. Melphalan remains the mainstay conditioning for multiple myeloma and lymphomas, and it has been used successfully in preparative regimens of a variety of other hematological and nonhematological malignancies. The addition of newer agents to conditioning, such as bortezomib or lenalidomide for myeloma or clofarabine for myeloid malignancies, may improve antitumor effects for transplantation, whereas melpha...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Lenalidomide/thalidomide: Interstitial pneumonitis: case report

(Source: Reactions)

Second malignancies in total therapy 2 and 3 for newly diagnosed multiple myeloma: influence of thalidomide and lenalidomide during maintenance

Thalidomide and lenalidomide constitute an important part of effective myeloma therapy. Recent data from the Intergroup Francophone du My&eacute;lome, Cancer and Leukemia Group B, and Gruppo Italiano Malattie Ematologiche dell Adulto MM-015 trials suggest that lenalidomide maintenance therapy is associated with a higher incidence of second primary malignancies (SPMs), including both hematologic and solid malignancies. In the present study, we analyzed data from the Total Therapy 2 (TT2) trial, along with the 2 Total Therapy 3 (TT3) trials. TT2 patients were assigned randomly to either a control group (no thalidomide) or to the experimental group (thalidomide during induction, between transplantations, and during consolidation and maintenance). The 2 TT3 trials used thalidomide and bortezom...

Long-term disease stabilization in a patient with castration-resistant metastatic prostate cancer by the addition of lenalidomide to low-dose dexamethasone and celecoxib.

Conclusion: The addition of lenalidomide to low-dose dexamethasone and celecoxib resulted in an impressive longterm disease stabilization of CRPC in this patient, allowing him to lead an active life with a good quality of life. PMID: 22868509 [PubMed - in process] (Source: Onkologie)

CEP-18770 (delanzomib) in combination with dexamethasone and lenalidomide inhibits the growth of multiple myeloma

Abstract: Preclinical and clinical studies have shown that proteasome inhibitors (PIs) have anti-MM activity in combination with dexamethasone or lenalidomide. However, no data exists on the anti-MM effects of combinations involving the PI delanzomib with dexamethasone and/or lenalidomide. Herein, we show that delanzomib in combination with dexamethasone and/or lenalidomide results in superior tumor reduction and extended tumor growth delays when compared to vehicle alone, these drugs alone, or the doublet of dexamethasone and lenalidomide. The favorable results obtained from the three xenograft studies suggest that delanzomib in combination with dexamethasone and lenalidomide should be explored for the treatment of MM. (Source: Leukemia Research)

Celgene Europe Ltd. has withdrawn its application to CHMP to use lenalidomide [Revlimid] for maintenance treatment of newly diagnosed

(Source: Reactions)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

A phase 1 study of concomitant high-dose lenalidomide and 5-azacitidine induction in the treatment of AML

Authors: G Ramsingh, P Westervelt, A F Cashen, G L Uy, K Stockerl-Goldstein, C N Abboud, N Bernabe, R Monahan, J F DiPersio & R Vij (Source: Leukemia)

Multiple inhibitory ligands induce impaired T-cell immunologic synapse function in chronic lymphocytic leukemia that can be blocked with lenalidomide: establishing a reversible immune evasion mechanism in human cancer

Cancer immune evasion is an emerging hallmark of disease progression. We have demonstrated previously that impaired actin polymerization at the T-cell immunologic synapse is a global immune dysfunction in chronic lymphocytic leukemia (CLL). Direct contact with tumor cells induces defective actin polarization at the synapse in previously healthy T cells, but the molecules mediating this dysfunction were not known. In the present study, we show via functional screening assays that CD200, CD270, CD274, and CD276 are coopted by CLL cells to induce impaired actin synapse formation in both allogeneic and autologous T cells. We also show that inhibitory ligand&ndash;induced impairment of T-cell actin dynamics is a common immunosuppressive strategy used by both hematologic (including lymphoma) and...

A phase II study of lenalidomide in patients with extranodal marginal zone B-cell lymphoma of the mucosa associated lymphoid tissue (MALT-lymphoma).

Authors: Kiesewetter B, Troch M, Dolak W, M√ľllauer L, Lukas J, Zielinski CC, Raderer M Abstract MALT lymphoma shares certain features with multiple myeloma. In view of this and the activity of lenalidomide in various B-cell lymphomas, we have initiated a phase II study of lenalidomide in patients with MALT lymphoma. Patients with histologically verified advanced MALT lymphoma were included in the study. Treatment consisted of lenalidomide 25 mg p.o. days 1-21, with a 7 day-break after each cycle. A total of 18 patients were included in the trial; 5 had gastric and 13 had extragastric MALT lymphoma, but two discontinued therapy during the first course of therapy.In the intent to treat analysis, an overall response rate of 61% was seen (11/18; 6 complete and 5 partial remissions). T...

The immunomodulatory agents lenalidomide and thalidomide for treatment of the myelodysplastic syndromes: A clinical practice guideline

Conclusions: Lenalidomide is recommended as first line therapy in lower risk del5q MDS. There is insufficient evidence to recommend lenalidomide for treatment of higher risk del5q MDS or AML, or for any risk non-del5q MDS or AML. Combining lenalidomide with other agents is not recommended. Thalidomide is not recommended. (Source: Critical Reviews in Oncology Hematology)

Biological Therapy Doublets: Pairing Rituximab with Interferon, Lenalidomide, and Other Biological Agents in Patients with Follicular Lymphoma

Abstract&nbsp;&nbsp;Rituximab (R) is a monoclonal antibody with high therapeutic efficacy in low-grade CD20+ lymphoma. The combination of R with chemotherapy is the most common treatment option for patients with follicular lymphoma (FL). The efficacy of R has also been shown to be augmented, when used in combinations with biologicals such as interferon-alpha-2a (IFN), bortezomib, or lenalidomide. The best combination of these drugs are not well defined and a better understanding of pharmacokinetics and timing of drugs relative to the rituximab infusion is crucial. Other new targeted agents, such as inhibitors of BTK and PI3Kdelta, have also been promising in FL. Translational research questions should be added to clinical trial protocols to increase the knowledge on how the tumor mic...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Single‚?źagent lenalidomide in relapsed/refractory mantle cell lymphoma: results from a UK phase II study suggest activity and possible gender differences

We present data from a phase II study investigating a novel treatment strategy for relapsed/refractory mantle cell lymphoma (MCL). Twenty‚?źsix patients received lenalidomide 25¬†mg/d (days 1‚??21 of a 28‚?źd cycle) for up to 6 cycles followed by low‚?źdose maintenance lenalidomide (15¬†mg) in responding patients. Eight patients achieved complete or partial response to give an overall response rate of 31% with median response duration of 22¬∑2¬†months [95% confidence interval (CI) 0¬∑0‚??53¬∑6] and median progression‚?źfree survival (PFS) of 3¬∑9¬†months (95% CI 0¬∑0‚??11¬∑1). An additional six patients (23%) achieved stable disease. Eleven patients received maintenance with median PFS of 14¬∑6¬†months (95% CI 7¬∑3‚??21¬∑9). Correlative studies showed that peripheral T and Natural Killer (...

Lenalidomide for Multiple Myeloma

New England Journal of Medicine, Volume 367, Issue 6, Page 573-575, August 2012. (Source: New England Journal of Medicine)

Diagnosis and therapy of myelodysplastic syndromes in Germany: a retrospective multicenter analysis.

Conclusion: While the WHO classification system is widely used in clinical practice, karyotyping and IPSS risk assessment do not seem to be common standard. Despite encouraging data on the use of effective and novel drugs, such as lenalidomide and azacitidine in MDS therapies, management of the disease could be further improved by more widespread use of risk stratification of patients using cytogenetics and IPSS assessment. PMID: 22722455 [PubMed - in process] (Source: Onkologie)

Multiple myeloma cells expressing low levels of CD138 have an immature phenotype and reduced sensitivity to lenalidomide.

Multiple myeloma cells expressing low levels of CD138 have an immature phenotype and reduced sensitivity to lenalidomide. Int J Oncol. 2012 Sep;41(3):876-84 Authors: Kawano Y, Fujiwara S, Wada N, Izaki M, Yuki H, Okuno Y, Iyama K, Yamasaki H, Sakai A, Mitsuya H, Hata H Abstract CD138 expression is a hallmark of plasma cells and multiple myeloma cells. However, decreased expression of CD138 is frequently observed in plasma cells of myeloma patients, although the clinical significance of this is unclear. To evaluate the significance of low expression of CD138 in MM, we examined the phenotypes of MM cells expressing low levels of CD138. Flow cytometric analysis of primary MM cells revealed a significant decrease in CD138 expression in patien...

Toxicity-reduced, myeloablative allograft followed by lenalidomide maintenance as salvage therapy for refractory/relapsed myeloma patients

Toxicity-reduced, myeloablative allograft followed by lenalidomide maintenance as salvage therapy for refractory&#47;relapsed myeloma patients Bone Marrow Transplantation advance online publication, August 6 2012. doi:10.1038/bmt.2012.142 Authors: N Kr&#246;ger, T Zabelina, E Klyuchnikov, M Kropff, K-H Pfl&#252;ger, A Burchert, T St&#252;big, C Wolschke, F Ayuk, Y Hildebrandt, U Bacher, A Badbaran, G Schilling, T Hansen, D Atanackovic & A R Zander (Source: Bone Marrow Transplantation)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Targeted Anti-Leukemic Therapy as Disease-Stabilizing Treatment for Leukemia Relapse after Allogeneic Stem Cell Transplantation: Will It Be Possible To Combine These Strategies with Retransplantation or Donor Lymphocyte Infusions?

Authors: Reikvam H, Kittang AO, Melve G, Mosevoll KA, Bentsen PT, Ersvær E, Gjertsen BT, Bruserud O Abstract Allogeneic stem cell transplantation is commonly used in the treatment of high-risk acute myeloid leukemia (AML). This intensive treatment has a high early transplant-related mortality, and an additional significant cause of death in these patients is later AML relapse. Retransplantation can be considered for a minority of patients, but only 10-20% of selected patients achieve long-term survival. Donor lymphocyte infusion (DLI) has an antileukemic effect, but the effect of this treatment usually lasts for only 3-4 months. A possible strategy to improve the prognosis could be to combine antileukemic T-cell therapy (i.e. DLI) with AML-targeting therapy. Several aspects have t...

Acetylon begins combination study of rocilinostat with revlimid, dexamethasone

Acetylon Pharmaceuticals has begun patient enrolment in a new Phase 1b trial of rocilinostat (ACY-1215) in combination with Celgene's revlimid (lenalidomide) and dexamethasone for patients with multiple myeloma. (Source: Drug Development Technology)

Lenalidomide enhancement of human T cell functions in human immunodeficiency virus (HIV)-infected and HIV-negative CD4 T lymphocytopenic patients.

Authors: Lim H, Kane L, Schwartz JB, Hesdorffer CS, Deeks SG, Greig N, Ferrucci L, Goetzl EJ Abstract Suppressed T cell functions in human immunodeficiency virus (HIV) infection were identified and corrected by lenalidomide in middle-aged HIV-infected patients. Chemotaxis of T cells from HIV-infected men (n‚??=‚??6, mean 43 years) to sphingosine 1-phosphate (S1P) and CCL21 was significantly lower than that of HIV-negative men (n‚??=‚??6, mean 41 years), and was enhanced significantly up to control levels by 100 and 1000‚??nM lenalidomide. Generation of interleukin (IL)-2, but not interferon (IFN)-ő≥, by T cells of middle-aged HIV-infected men was significantly lower than that for controls and was increased significantly by 10-1000‚??nM lenalidomide up to a maximum of more than 300%...

Lenalidomide: Interstitial pneumonitis in an elderly patient: case report

(Source: Reactions)

Lenalidomide: Interstitial pneumonitis: case report

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Venous thromboembolism in cancer patients - Risk scores and recent randomised controlled trials.

Authors: Thaler J, Ay C, Pabinger I Abstract Cancer patients are at increased risk of developing venous thromboembolism (VTE). Guidelines recommend routine thromboprophylaxis in hospitalised acutely ill cancer patients and in myeloma patients receiving combination treatments including thalidomide or lenalidomide. Currently, thromboprophylaxis is not recommended in cancer outpatients. It is the aim of this review to give an overview of studies that applied scores for the risk assessment of cancer-related VTE. We will also discuss randomised controlled trials (RCTs) that investigated primary thromboprophylaxis in cancer patients. Recently, Khorana et al. published a practical and reproducible risk assessment score that includes clinical and laboratory parameters for the stratificatio...

Epigenetic induction of adaptive immune response in multiple myeloma: sequential azacitidine and lenalidomide generate cancer testis antigen‚?źspecific cellular immunity

SummaryPatients with multiple myeloma (MM) undergoing high dose therapy and autologous stem cell transplantation (SCT) remain at risk for disease progression. Induction of the expression of highly immunogenic cancer testis antigens (CTA) in malignant plasma cells in MM patients may trigger a protective immune response following SCT. We initiated a phase II clinical trial of the DNA hypomethylating agent, azacitidine (Aza) administered sequentially with lenalidomide (Rev) in patients with MM. Three cycles of Aza and Rev were administered and autologous lymphocytes were collected following the 2nd and 3rd cycles of Aza‚?źRev and cryopreserved. Subsequent stem cell mobilization was followed by high‚?źdose melphalan and SCT. Autologous lymphocyte infusion (ALI) was performed in the second mont...

Novel lenalidomide-based combinations for treatment of multiple myeloma

Abstract: Lenalidomide (LEN) is an immunomodulatory drug (IMiD) which exerts tumoricidal effects and has immunomodulatory, anti-inflammatory and anti-angiogenic properties that synergistically keep the tumor in remission. It is currently approved as second-line therapy for multiple myeloma (MM) and for 5q defective myelodysplastic syndrome, while ongoing studies are at present evaluating its role in both solid and hematologic malignancies. Based on its high activity as an anti-myeloma drug with a good tolerability profile, LEN is currently gaining interest in both preclinical and clinical research for combinatory treatments with novel agents including monoclonal antibodies, immunotoxins, tyrosine kinase inhibitors, new proteasome inhibitors and epigenetic-interfering agents as well as with...

Myeloma Drug Gets Accelerated FDA Approval

The FDA has granted accelerated approval to a new myeloma drug called carfilzomib. The approval is for use in patients with myeloma who have relapsed or did not respond to at least two previous types of therapy including bortezomib (Velcade) and thalidomide or lenalidomide. &#160;Eligible patients must also have shown a progression in their disease within 60 days of completing their last therapy....Read Full Post (Source: About.com Lymphoma)

A Model of Translational Cancer Research in Multiple Myeloma

AbstractRecently, intensive laboratory and preclinical studies have identified and validated therapeutic molecular targets in multiple myeloma (MM). The introduction of novel agents such as the proteasome inhibitor bortezomib and the immunomodulatory drugs thalidomide and lenalidomide, which were rapidly translated from preclinical studies at the Dana‚?źFarber Cancer Institute (DFCI) into clinical trials, has changed the treatment paradigm and markedly extended overall survival; MM has therefore become a remarkable example of translational cancer research in new drug development.In this article, with the aim of determining the key factors underlying success in translational research, we focus on our studies of MM at DFCI as well as at our institutes. The identification of these key factors...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

POEMS syndrome: Update on diagnosis, risk‚?źstratification, and management

AbstractDisease overview: POEMS syndrome is a paraneoplastic syndrome due to an underlying plasma cell neoplasm. The major criteria for the syndrome are polyradiculoneuropathy, clonal plasma cell disorder (PCD), sclerotic bone lesions, elevated vascular endothelial growth factor, and the presence of Castleman disease. Minor features include organomegaly, endocrinopathy, characteristic skin changes, papilledema, extravascular volume overload, and thrombocytosis. Diagnoses are often delayed because the syndrome is rare and can be mistaken for other neurologic disorders, most commonly chronic inflammatory demyelinating polyradiculoneuropathy. POEMS syndrome should be distinguished from the Castleman disease variant of POEMS syndrome, which has no clonal PCD and typically little to no peripher...

Anaplastic large cell lymphoma, ALK-negative

Abstract: Anaplastic large cell lymphoma (ALCL), anaplastic lymphoma kinase (ALK)-negative (ALCL-ALK‚??) is a provisional entity in the WHO 2008 Classification that represents 2‚??3% of NHL and 12% of T-cell NHL. No particular risk factor has been clearly identified for ALCL, but a recent study showed an odds ratio of 18 for ALCL associated with breast implants. Usually, the architecture of involved organs is eroded by solid, cohesive sheets of neoplastic cells, with peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) and classical Hodgkin lymphoma being the main differential diagnoses. In this regard, staining for PAX5 and CD30 is useful. Translocations involving ALK are absent, TCR genes are clonally rearranged. CGH and GEP studies suggest a tendency of ALCL-ALK‚?? to differ bo...

(Bortezomib plus lenalidomide/thalidomide)- vs (bortezomib or lenalidomide/thalidomide)-containing regimens as induction therapy in newly diagnosed multiple myeloma: a meta-analysis of randomized controlled trials

Abstract&nbsp;&nbsp;The aim of the study was to perform a meta-analysis of the efficacy and safety of (bortezomib plus lenalidomide/thalidomide)- vs (bortezomib or lenalidomide/thalidomide)-containing regimens as induction therapy in newly diagnosed multiple myeloma. We searched electronic and printed sources for relevant articles published. Inclusion criteria was as follows: randomized controlled trials (RCT) of (bortezomib plus lenalidomide/thalidomide) vs (bortezomib or lenalidomide/thalidomide)-containing regimens as induction therapy in newly diagnosed multiple myeloma. Two reviewers independently assessed potentially eligible studies and extracted relevant data. We retrieved five RCT studies including a total of 1,200 patients. Using the random-effects model to pool the five RC...

Imaging Features of Extramedullary, Relapsed, and Refractory Multiple Myeloma involving the Liver Across Treatment With Cyclophosphamide, Lenalidomide, Bortezomib, and Dexamethasone [DIAGNOSIS IN ONCOLOGY]

(Source: Journal of Clinical Oncology)

Lenalidomide enhancement of human T cell functions in human immunodeficiency virus (HIV)‚?źinfected and HIV‚?źnegative CD4 T lymphocytopenic patients

SummarySuppressed T cell functions in human immunodeficiency virus (HIV) infection were identified and corrected by lenalidomide in middle‚?źaged HIV‚?źinfected patients. Chemotaxis of T cells from HIV‚?źinfected men (n‚??=‚??6, mean 43 years) to sphingosine 1‚?źphosphate (S1P) and CCL21 was significantly lower than that of HIV‚?źnegative men (n‚??=‚??6, mean 41 years), and was enhanced significantly up to control levels by 100 and 1000‚??nM lenalidomide. Generation of interleukin (IL)‚?ź2, but not interferon (IFN)‚?źő≥, by T cells of middle‚?źaged HIV‚?źinfected men was significantly lower than that for controls and was increased significantly by 10‚??1000‚??nM lenalidomide up to a maximum of more than 300%. CD4 and CD8 T cells isolated from healthy middle‚?źaged men and reconstituted in ...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

The role of novel agents on the reversibility of renal impairment in newly diagnosed symptomatic patients with multiple myeloma

Authors: M A Dimopoulos, M Roussou, M Gkotzamanidou, N Nikitas, E Psimenou, D Mparmparoussi, C Matsouka, M Spyropoulou-Vlachou, E Terpos & E Kastritis (Source: Leukemia)

Relapsed Multiple Myeloma: Who Benefits from Salvage Autografts?

Conclusions:‚?? Salvage ASCT is an effective and safe treatment option in selected patients and should be considered in patients relapsing &gt; 36 months after their initial ASCT. The time‚?źdependent relationship between PFI and salvage ASCT outcome is important when stratifying patient groups who may benefit from this procedure. (Source: Internal Medicine Journal)

Lenalidomide in combination with dexamethasone improves survival and time-to-progression in patients ‚?•65¬†years old with relapsed or refractory multiple myeloma.

Authors: Chanan-Khan AA, Lonial S, Weber D, Borrello I, Fo√† R, Hellmann A, Dimopoulos M, Swern AS, Knight R Abstract Two pivotal, phase III, randomised, placebo-controlled, registration trials (MM-009 and MM-010) showed that lenalidomide plus dexamethasone was more effective than placebo plus dexamethasone in the treatment of patients with relapsed or refractory multiple myeloma. This pooled, retrospective subanalysis of MM-009 and MM-010 analysed outcomes according to patient age. A total of 704 patients (390 aged &lt;65¬†years, 232 aged 65-74¬†years, and 82 aged ‚?•75¬†years) received lenalidomide or placebo, both in combination with dexamethasone. The overall response rate (ORR) was significantly higher in patients treated with lenalidomide plus dexamethasone versus placebo plu...

Thalidomide: chemistry, therapeutic potential and oxidative stress induced teratogenicity.

Authors: Kumar N, Sharma U, Singh C, Singh B Abstract Thalidomide and its one analogue, lenalidomide (CC5103 or revlimid) are recently approved for the treatment of multiple myeloma. Multiple myeloma is characterized by an overproduction of malignant plasma cells in the bone marrow. The journey of thalidomide was started in 1956 when it was marketed as a non-barbiturate sedative agent. It was considered as a "wonder drug" that provided safe and sound sleep and hence, used to cure morning sickness in pregnant women. Later, in 1961, it was withdrawn from the world market due to its serious side effects, i.e., teratogenic activity. However, the recent decade has witnessed a true renaissance in interest in its broad biological activity. In particular, thalidomide was reevaluated and at...

Light chain deposition disease affecting the gastrointestinal tract in the setting of post-living donor kidney transplantation.

We report a case of LCDD in living related kidney transplant recipient presenting with severe GI dysmotility, weight loss and progressive allograft dysfunction. A diagnosis of LCDD was based on the kidney biopsy findings in the failing renal allograft, along with the presence of excess serum free kappa light chains and abnormal kappa:lambda ratio. Subsequent review of GI biopsies confirmed kappa light chain immunoglobulin deposition within the stomach. Further investigation suggested additional hepatic and cardiac involvement. The patient went on to receive bortezomib, achieving a biochemical response and stabilization of his advanced renal dysfunction; however, bortezomib was discontinued due to toxicity. The patient was subsequently treated with lenalidomide and dexamethasone, which were...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Phase 1b study of lenalidomide in combination with rituximab-CHOP (R2-CHOP) in patients with B-cell lymphoma

Authors: H Tilly, F Morschhauser, G Salles, R-O Casasnovas, P Feugier, T J Molina, F Jardin, L Terriou, C Haioun & B Coiffier (Source: Leukemia)

Lenalidomide enhances anti-myeloma cellular immunity

Abstract&nbsp;&nbsp;Lenalidomide is an effective therapeutic agent for multiple myeloma that exhibits immunomodulatory properties including the activation of T and NK cells. The use of lenalidomide to reverse tumor-mediated immune suppression and amplify myeloma-specific immunity is currently being explored. In the present study, we examined the effect of lenalidomide on T-cell activation and its ability to amplify responses to a dendritic cell-based myeloma vaccine. We demonstrate that exposure to lenalidomide in the context of T-cell expansion with direct ligation of CD3/CD28 complex results in polarization toward a Th1 phenotype characterized by increased IFN-ő≥, but not IL-10 expression. In vitro exposure to lenalidomide resulted in decreased levels of regulatory T cells and a de...

Infections in myelodysplastic syndromes: a review.

Authors: Toma A, Fenaux P, Dreyfus F, Cordonnier C Abstract Myelodysplastic syndromes are associated with a risk of severe infections. While neutropenia is likely the main predisposing factor, several other immune defects have been reported, including impaired neutrophil function, B-, T-, and NK-cell defects and the possible consequences of iron overload due to red blood cell transfusions. The advanced age of most patients, their frequent comorbidities and the fact that drugs like hypomethylating agents and lenalidomide, which are effective in myelodysplastic syndromes but can transiently worsen neutropenia, may increase the risk of infection and their severity in this context. A majority of infections in myelodysplastic syndromes are bacterial, while the incidence of fungal infect...

Celgene Europe Limited withdraws its application for an extension of the indication for lenalidomide (Revlimid¬ģ)

Source: European Medicines Agency (EMA) Area: News The European Medicines Agency has been formally notified by Celgene Europe Limited of its decision to withdraw its application for the centrally authorised medicine lenalidomide (Revlimid ¬ģ ) for an extension of the therapeutic indication in patients with newly diagnosed multiple myeloma and for the addition of new pack sizes. The company had submitted an application in December 2010 for a variation of the marketing authorisation for the drug to extend the indication to maintenance treatment of newly diagnosed multiple myeloma patients who have not progressed following initial treatment with melphalan, prednisone and lenalidomide or following autologous stem cell transplantation. &#160; &#160; The variation in the licence ...

Horizon scanning: FDA advisory panel supports approval of carfilzomib for previously treated relapsed and refractory multiple myeloma

Source: BioSpace Area: News BioSpace reports that the United States Food and Drug Administration's (FDA) Oncologic Drugs Advisory Committee (ODAC) has voted 11-0 [with 1 abstention] that, in patients with relapsed and refractory multiple myeloma who have received at least two prior lines of therapy that included a proteasome inhibitor and an immunomodulatory agent (IMiD), the benefit-risk assessment is favourable for the use of carfilzomib (Kyprolis¬ģ). &#160; The New Drug Application submitted to the FDA is based on an open-label, single-arm Phase 2b trial and supportive data from additional studies. The open label study evaluated 266 heavily-pre treated patients with relapsed and refractory multiple myeloma who had received at least two prior therapies, including bortezomib and eit...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Revlimid (lenalidomide) Extension Of Indication Submission Withdrawn, Europe

The European Medicines Agency has been informed by Celgene Europe Limited that it has withdrawn its submission for approval for Revlimid (lenalidomide) - an application for an extension of the therapeutic indication in newly diagnosed multiple myeloma (blood cancer) patients, as well as new pack sizes had been sought. Business analysts say this is a setback for Celgene Europe's best-selling medication, which was expected to grow... (Source: Health News from Medical News Today)

Bortezomib Combination Therapy in Multiple Myeloma

Bortezomib was approved for the treatment of multiple myeloma (MM) in 2003. Since then several bortezomib-based combination therapies have emerged. Although some combinations have been preceded by preclinical investigations, most have followed the inevitable process in which active (or potentially active) drugs are combined with each other to create new treatment regimens. Regimens that have combined bortezomib with corticosteroids, alkylating agents, thalidomide, and/or lenalidomide have resulted in high response rates. Despite the higher and often deeper response rates and prolongation of progression-free survival with bortezomib-based multiagent regimens, an overall survival (OS) advantage has not been demonstrated with most combinations compared to the sequential approach of using anti...

Blood Cancer Shockers: Celgene Dives While Onyxx Soars

This morning, Celgene pulled its application to have its blood cancer drug Revlimid approved for maintenance use in newly diagnosed patients with multiple myeloma. This would have dramatically expanded the use of the medicine, which is already one of the standard treatments for the blood cancer. (Source: Forbes.com Healthcare News)

Voice of Patients Critical in Championing Life Saving Drugs

  &mdash;Positive Development for Carfilzomib after Emotional Testimony by IMF Representatives&mdash; &mdash;Decision about REVLIMID Approval in Newly Diagnosed Patients Delayed in Europe&#8212; &mdash;Pomalidomide Application Accepted by FDA and will be Submitted in Europe&mdash; (Source: International Myeloma Foundation)

Lenalidomide augments the efficacy of bacillus Calmette-Guerin (BCG) immunotherapy in vivo

Conclusions: The immunomodulatory molecule lenalidomide augments the response to BCG in an in vivo mouse model. This provides the rationale for studying the combination in patients with high grade NMIBC. (Source: Urologic Oncology: Seminars and Original Investigations)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Lenalidomide in Combination With Rituximab for Patients With Relapsed or Refractory Mantle-Cell Lymphoma: A Phase 1/2 Clinical Trial

Results of this phase I/II trial of patients with relapsed/refractory mantle cell lymphoma treated with escalating doses of lenalidomide and standard-dose rituximab showed 57% overall response, with complete... (Source: OncologySTAT Journal Scans)

Second Malignancies in Total Therapy 2 and 3 for Newly diagnosed Multiple Myeloma: Influence of Thalidomide and Lenalidomide During Maintenance

Analysis of three large trials found cumulative incidence of second primary malignancies (SPM) did not differ significantly between either thalidomide or lenalidomide maintenance in myeloma when measured... (Source: OncologySTAT Journal Scans)

A Phase 1/2 Study of Carfilzomib in Combination With Lenalidomide and Low-Dose Dexamethasone as a Frontline Treatment for Multiple Myeloma

Results of this phase I/II trial of patients with newly diagnosed myeloma treated with carfilzomib, in combination with lenalidomide and low-dose dexamethasone, showed near complete response in 62% of... (Source: OncologySTAT Journal Scans)

European perspective on multiple myeloma treatment strategies: update following recent congresses.

This article presents an update to a previous review of European treatment practices and is based on discussions during an expert meeting that was convened to review novel agent data published or presented at medical meetings until the end of 2011 and to assess their impact on treatment strategies. PMID: 22573721 [PubMed - in process] (Source: The Oncologist)

Carfilzomib Combo Achieves High Response in Multiple MyelomaCarfilzomib Combo Achieves High Response in Multiple Myeloma

In an extended trial of carfilzomib in combination with lenalidomide plus dexamethasone, 61% of patients achieved a stringent complete response after 8 cycles. Medscape Medical News (Source: Medscape Medical News Headlines)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Lenalidomide augments the efficacy of bacillus Calmette-Guerin (BCG) immunotherapy in vivo.

CONCLUSIONS: The immunomodulatory molecule lenalidomide augments the response to BCG in an in vivo mouse model. This provides the rationale for studying the combination in patients with high grade NMIBC. PMID: 22717623 [PubMed - as supplied by publisher] (Source: Urologic Oncology)

Impact of lenalidomide on the functional properties of human mesenchymal stromal cells

Conclusion: LEN can modulate the expression of cell surface molecules and the chemokine secretion of MSCs in vitro. These effects might contribute to the clinical effects of the compound in vivo for patients with hematological malignancies. (Source: Experimental Hematology)

Novel Agents in Hodgkin Lymphoma

Abstract&nbsp;&nbsp;Despite the success of modern therapy for Hodgkin lymphoma (HL), about 15&nbsp;% of patients will fail both first-line and second-line therapy and treatment options for these patients are limited. New agents are needed to improve the outcome for relapsed or refractory HL and to improve the toxicity of current front-line regimens. Brentuximab vedotin (BV) was recently approved for HL and is likely to have a tremendous impact on the current treatment paradigm for HL. Additional agents that have demonstrated activity in HL include histone deacetylase inhibitors, such as panobinostat, entinostat, and mocetinostat, PI3-kinase/Akt/Mtor pathway inhibitors, such as everolimus, as well as lenalidomide and bendamustine. Studies evaluating these agents alone or in combinatio...

Myelodysplastic syndromes: 2012 update on diagnosis, risk‚?źstratification, and management

AbstractDisease Overview: The myelodysplastic (MDS) are a very heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increased risk of transformation to acute myelogenous leukemia (AML). MDS occurs more frequently in older male and in individuals with prior exposure to cytotoxic therapy.Diagnosis: Diagnosis of MDS is based on morphological evidence of dysplasia upon visual examination of a bone marrow aspirate and biopsy. Information obtained from additional studies such as karyotype, flow cytometry or molecular genetics is complementary but not diagnostic.Risk‚?źstratification: Prognosis of patients with MDS can be calculated using a number of scoring systems. In general, all these scoring systems include analysis of peripheral cytopenias, percentage of...

Exploiting Synthetic Lethality for the Therapy of ABC Diffuse Large B Cell Lymphoma

Yibin Yang, Arthur L. Shaffer, N.C. Tolga Emre, Michele Ceribelli, Meili Zhang, George Wright, Wenming Xiao, John Powell, John Platig, Holger Kohlhammer, Ryan M. Young, Hong Zhao, Yandan Yang, Weihong Xu, Joseph J. Buggy, Sriram Balasubramanian, Lesley A. Mathews, Paul Shinn, Rajarshi Guha, Marc Ferrer, Craig Thomas, Thomas A. Waldmann, Louis M. Staudt. Knowledge of oncogenic mutations can inspire therapeutic strategies that are synthetically lethal, affecting cancer cells while sparing normal cells. Lenalidomide is an active agent in the activat.... (Source: Cancer Cell)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

ASCO: Drug Combo Helps in Multiple Myeloma

CHICAGO (MedPage Today) -- Multiple myeloma patients whose disease is not controlled by lenalidomide (Revlimid) or bortezomib (Velcade) appear to respond to treatment with pomalidomide (Actimid) plus dexamethasone, researchers reported here. (Source: MedPage Today Primary Care)

New Frontline Treatment Regimen For Multiple Myeloma

Results from a study published online in Blood, the Journal of the American Society of Hematology (ASH), demonstrate that inclusion of carfilzomib, a novel targeted therapy for multiple myeloma, in combination with lenalidomide and low-dose dexamethasone, resulted in complete or near complete remission in a majority of patients with newly diagnosed multiple myeloma. Multiple myeloma is cancer of the plasma cells, the white blood cells in the bone marrow that normally produce infection-fighting antibodies... (Source: Health News from Medical News Today)

A phase 1/2 study of lenalidomide with low-dose oral cyclophosphamide and low-dose dexamethasone (RdC) in AL amyloidosis

This study is registered at www.clinicaltrials.gov as NCT00981708. (Source: Blood)

Targeted therapy of multiple myeloma: the changing paradigm at the beginning of the new millennium.

Authors: Morabito F, Recchia AG, Mazzone C, Gentile M Abstract Multiple myeloma (MM) is a malignant hematological neoplasmand constitutes 10% of blood cancers. Recently, it has become evident that almost all cases of MM are preceded by gammopathy of undetermined significance (MGUS). MM is diagnosed by the presence of paraprotein in serum or urine, detected by serum electrophoresis and immunofixation, infiltration of malignant plasma cells in the bone marrow and related organ, or tissue damage. Cytogenetic status, International Staging System (ISS) and the quality of response to therapy are the most important prognostic factors. In the last decade the availability of new effective drugs, such as thalidomide, lenalidomide and bortezomib have provided a new therapeutic scenario expect...

Novel targets and derived small molecule inhibitors in multiple myeloma.

Authors: Podar K Abstract Recent research advances have defined a key role of the bone marrow (BM) in multiple myeloma (MM) pathogenesis thereby leading to new treatment paradigms, which aim to target both the tumor cell as well as its BM microenvironment. The incorporation of thalidomide, bortezomib, and lenalidomide into conventional cytotoxic and transplantation regimens in relapsed and refractory, but also in newly diagnosed MM has changed treatment options during the last decade. However, MM remains still incurable. Ongoing translational research aims to identify additional therapeutic targets and to design derived agents, predominantly small molecule inhibitors, with higher potency and less toxicity to further improve MM patient outcome and to overcome drug resistance. PM...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Carfilzomib demonstrates efficacy as new frontline treatment regimen for multiple myeloma

(American Society of Hematology) Results from a study published online today in Blood, the Journal of the American Society of Hematology, demonstrate that inclusion of carfilzomib, a novel targeted therapy for multiple myeloma, in combination with lenalidomide and low-dose dexamethasone, resulted in complete or near complete remission in a majority of patients with newly diagnosed multiple myeloma. (Source: EurekAlert! - Cancer)

Lenalidomide, Both as Single-Agent and Combined With Rituximab, Beneficial in Patients With Recurrent Follicular Lymphoma

Capsule Summary - In this randomized phase II trial, ORR was higher and EFS was longer with rituximab plus lenalidomide vs lenalidomide alone in patients with follicular lymphoma who experienced relapse after at least 1 previous rituximab-based treatment regimen. (Source: Clinical Care Options Oncology - Lymphoma)

Infection complications in an unselected cohort of patients with Multiple Myeloma treated with lenalidomide combinations

Immunomodulatory drugs (IMiDs) exert various effects on the immune system, altering cytokine production, regulating T cell costimulation and enhancing NK cell cytotoxicity. Particularly, IMiDs inhibit tumour necrosis factor‚?źalfa (TNF‚?źalfa), playing an important role in immune response against bacterial and virus infections [1]. Moreover, lenalidomide causes myelosuppression, mainly neutropenia, that is an important risk factor for infections.¬© 2012 John Wiley & Sons A/S (Source: European Journal of Haematology)

Clinical trials

The U.S. Food and Drug Administration (FDA) is informing the public of an increased risk of second primary malignancies in patients with newly-diagnosed multiple myeloma who received Revlimid (lenalidomide). (Source: Modern Medicine)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

The emerging role of lenalidomide in the management of mantle cell lymphoma (MCL)

Mantle cell lymphoma (MCL) is considered an aggressive and incurable B-cell malignancy despite current available treatments that include the incorporation of rituximab, bortezomib, high-dose cytarabine, and for those eligible, high dose chemotherapy and autologous bone marrow transplant (HDC-ASCT). Patients with relapsed/refractory MCL represent a challenge for the treating physician stressing the need to develop therapeutic agents. Lenalidomide, a novel inmmunomodulatory drug (IMiD), is a promising therapeutic strategy for patients with relapsed/refractory B-cell lymphoma. Biologically, the mechanisms responsible for lenalidomide activity are yet to be clearly defined. Based on pre-clinical models and early correlative studies conducted parallel to clinical trials, lenalidomide has been f...

Autologous transplantation and management of younger patients with mantle cell lymphoma

Mantle cell lymphoma is traditionally conceived as one of the NHL subtypes with the worst prognosis and incurable. In responders to frontline induction with CHOP-like chemotherapy autologous stem cell transplantation (ASCT) is proven superior to interferon maintenance, but does not lead to long-term disease control. The efficacy of CHOP as induction therapy before ASCT in MCL is questioned and there is now evidence that as pretreatment before ASCT, AraC + rituximab leads to deeper remission and prolongs progression-free survival compared to rituximab + CHOP. The treatment goal of complete clinical and molecular remission in younger patients with MCL, is now within reach, based on an integrated approach of intensive AraC containing immunochemotherapy with or without subsequent ASCT, and...

Novel and emerging drugs for acute myeloid leukemia.

Authors: Stein EM, Tallman MS Abstract Acute myeloid leukemia (AML) is a challenging disease to treat with the majority of patients dying from their illness. While overall survival has been markedly prolonged in acute promyelocytic leukemia (APL), survival in younger adults with other subtypes of AML has only modestly improved over the last twenty years. Physicians who treat AML eagerly await drugs like Imatinib for chronic myeloid leukemia, Cladribine for hairy cell leukemia, and Rituximab for non-Hodgkin Lymphoma which have had an important impact on improving outcome. Recent research efforts have focused on refining traditional chemotherapeutic agents to make them more active in AML, targeting specific genetic mutations in myeloid leukemia cells, and utilizing novel agents such ...

Re‚?źevaluation of prognostic markers including staging, serum free light chains or their ratio and serum lactate dehydrogenase in multiple myeloma patients receiving novel agents

In conclusion, patients gaining the most from NA are those with an aggressive disease as reflected by advanced stage, abnormal LDH and high sFLCR. In addition, the adverse impact of these three variables is obscured by NA. Copyright © 2012 John Wiley & Sons, Ltd. (Source: Hematological Oncology)

[News] Lenalidomide maintenance for multiple myeloma

Three phase 3 randomised controlled trials have shown that patients with multiple myeloma receiving lenalidomide as maintenance therapy had significantly increased progression-free survival (PFS) and, in one study, improved overall survival. In two post-transplant trials, lenalidomide produced median PFS of 39 and 41 months versus 21 and 23 months for placebo, and in a third study in older, transplant-ineligible patients, a PFS of 31 versus 13 months for placebo. ‚??These studies clearly demonstrate that adding lenalidomide as maintenance gives patients another 6‚??10 months of remission‚?Ě, said Antonio Palumbo (University of Turin, Turin, Italy), lead investigator of the non-transplant study. (Source: The Lancet Oncology)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Perifosine plus lenalidomide and dexamethasone in relapsed and relapsed/refractory multiple myeloma: a Phase I Multiple Myeloma Research Consortium study

Elotuzumab in Combination With Lenalidomide and Low-Dose Dexamethasone in Relapsed or Refractory Multiple Myeloma [Hematologic Malignancies]

Conclusion The combination of elotuzumab, lenalidomide, and low-dose dexamethasone was generally well tolerated and showed encouraging response rates in patients with relapsed or refractory MM. (Source: Journal of Clinical Oncology)

Combination of low doses of Enzastaurin and Lenalidomide has synergistic activity in B-non-Hodgkin lymphoma cell lines

Abstract&nbsp;&nbsp;Less toxic and more active treatments are needed for indolent lymphomas as there is no curative treatment, and patients eventually die due to complications related to their disease. The purpose of the present study was to assess the antitumour activity of the combination of low doses of Enzastaurin and Lenalidomide (Revlimid) on B-lymphoma cell lines. The combination of Enzastaurin and Lenalidomide, at doses as low as 1 őľM, showed strong synergism against indolent lymphomas by reducing cell growth, producing an increase in G0‚??G1 phase followed by significant decrease in S phase, increasing apoptosis, and inhibiting PI3K/AKT, PKC and MAPK/ERK pathways. These preclinical findings, together with promising results obtained with Lenalidomide for the treatment of non...

Lenalidomide, cyclophosphamide, and dexamethasone (CRd) for light-chain amyloidosis: long-term results from a phase 2 trial

Light-chain (AL) amyloidosis remains incurable despite recent therapeutic advances. Given the activity of the lenalidomide-alkylating agent combination in myeloma, we designed this phase 2 trial of lenalidomide, cyclophosphamide, and dexamethasone in AL amyloidosis. Thirty-five patients, including 24 previously untreated, were enrolled. Nearly one-half of the patients had cardiac stage III disease and 28% had &ge; 3 organs involved. The overall hematologic response (&ge; partial response [PR]) rate was 60%, including 40% with very-good partial response or better. Using serum-free light chain for assessing response, 77% of patients had a hematologic response. Organ responses were seen in 29% of patients and were limited to those with a hematologic response. The median hematologic progressio...

The US FDA has made updates to the Revlimid [lenalidomide] label, similar to those announced recently by Health Canada.

(Source: Reactions)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Lenalidomide: Stevens-Johnson syndrome in an elderly patient: case report

(Source: Reactions)

Treatment with lenalidomide and dexamethasone in patients with multiple myeloma and renal impairment

Abstract: Renal impairment (RI) is a common complication affecting patients with multiple myeloma (MM). Timely identification of MM-related RI and early treatment with novel antimyeloma agents can reverse renal damage in a high proportion of patients and improve outcomes. The IMiDs¬ģ immunomodulatory compound lenalidomide (Len) in combination with dexamethasone (Dex) is an effective and well-tolerated regimen for patients with relapsed or refractory (RR) MM. A retrospective analysis of Phase III data has shown that Len/Dex remains effective and well-tolerated in patients with moderate or severe RI, albeit with an increase in myelosuppression. This analysis demonstrated that in a high proportion of patients Len/Dex treatment can reverse MM-related RI and restore normal function. Lenalidomid...

Lenalidomide Maintenance for Multiple Myeloma Improves Survival

Three studies published this week show that lenalidomide improves progression-free and overall survival as a maintenance therapy in multiple myeloma, despite its link to other primary cancers. (Source: Cancer Network)

Celgene Inc. has added new safety information to the Canadian Product Monograph of Revlimid [lenalidomide]

(Source: Reactions)

Combination of bendamustine, lenalidomide, and dexamethasone (BLD) in patients with relapsed or refractory multiple myeloma is feasible and highly effective: results of phase 1/2 open-label, dose escalation study

This study is registered at www.clinicaltrials.gov as #NCT01042704. (Source: Blood)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

RhoH is critical for cell-microenvironment interactions in chronic lymphocytic leukemia in mice and humans

Trafficking of B-cell chronic lymphocytic leukemia (CLL) cells to the bone marrow and interaction with supporting stromal cells mediates important survival and proliferation signals. Previous studies have demonstrated that deletion of Rhoh led to a delayed disease onset in a murine model of CLL. Here we assessed the impact of RhoH on homing, migration, and cell-contact dependent interactions of CLL cells. Rhoh&ndash;/&ndash; CLL cells exhibited reduced marrow homing and subsequent engraftment. In vitro migration toward the chemokines CXCL12 and CXCL13 and cell-cell interactions between Rhoh&ndash;/&ndash; CLL cells and the supporting microenvironment was reduced. In the absence of RhoH the distribution of phosphorylated focal adhesion kinase, a protein known to coordinate activation of the...

The Potential Beneficial Effects of Drugs on the Immune Response to Vaccination

Many immunotherapeutic agents in phase II cancer studies have given optimistic results, which were not confirmed in larger randomized studies. Here we explore the evidence that, contrary to previous opinion, many chemotherapeutic agents and other classes of drugs may enhance the response to therapeutic vaccines by reducing inflammation and/or by inhibiting regulatory T lymphocytes or myeloid-derived suppressor cells. In addition, some of these agents, such as the immunomodulatory drugs, may produce marked costimulatory activities as in the case of lenalidomide, which also has marked anti-inflammatory properties. With the first approval for a vaccine-based therapy for prostate cancer, we propose that many more vaccines will be able to achieve approval, especially when combined with the opti...

Lenalidomide benefits in multiple myeloma reported

Lenalidomide maintenance following melphalan‚??prednisone‚??lenalidomide induction appears to significantly lengthen progression-free survival in newly diagnosed multiple myeloma patients deemed unsuitable for transplantation, study findings suggest. (Source: MedWire News - Oncology)

Lenalidomide in solid tumors

Conclusion&nbsp;&nbsp;Monitoring of blood counts and for evidence of thromboembolic events is essential for patients treated with lenalidomide. Ongoing trials of lenalidomide combination therapy offer a treatment option for patients with advanced cancer and will better define the role of lenalidomide in solid tumors. Content Type Journal ArticleCategory Review ArticlePages 1-14DOI 10.1007/s00280-012-1874-2Authors Angela Segler, Department of Investigational Cancer Therapeutics, Phase I Clinical Trials Program, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 455, Houston, TX 77030, USAApostolia-Maria Tsimberidou, Department of Investigational Cancer Therapeutics, Phase I Clinical Trials Program, The University of Texas MD Anderson Cancer Center,...

Promising early results from drug combo for advanced multiple myeloma

NEW YORK (Reuters Health) - More than 80% of patients with advanced multiple myeloma responded to elotuzumab plus lenalidomide and low-dose dexamethasone in a phase I study. (Source: Modern Medicine)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Lenalidomide prolongs disease control for multiple myeloma patients after stem cell transplant

(Oregon Health & Science University) Multiple myeloma patients are better equipped to halt progression of this blood cancer if treated with lenalidomide, or Revlimid, following a stem cell transplant, according to a study co-authored by a physician with the Oregon Health & Science University Knight Cancer Institute. (Source: EurekAlert! - Cancer)

Chronic GVHD: Where are we? Where do we want to be? Will IMiDs help?

Chronic GVHD: Where are we&#63; Where do we want to be&#63; Will IMiDs help&#63; Bone Marrow Transplantation advance online publication, May 14, 2012. doi:10.1038/bmt.2012.76 Authors: Y P L Linhares, S Pavletic & R P Gale (Source: Bone Marrow Transplantation)

Three Studies Published in New England Journal of Medicine Aimed to Clarify the Efficacy and Safety of Lenalidomide Maintenance Therapy in Multiple Myeloma, in Both Post-Transplant and Non-Transplant Settings

Three randomized placebo-controlled trials examining the role of lenalidomide maintenance in multiple myeloma demonstrated significant benefits in progression-free survival, but only one trial demonstrated... (Source: OncologySTAT Journal Scans)

Long Term Lenalidomide Improves Myeloma Outcomes

A new study that has come out today in The New England Journal of Medicine has shown positive results in the treatment of myeloma. Researchers at the University of North Carolina set out to discover a way to prolong progression free survival in myeloma patients who have received an autologous stem cell transplant. Autologous stem cell transplant is a treatment option for many individuals with myeloma, and while it is an effective therapy, it is not curative. The disease will continue to progress over time....Read Full Post (Source: About.com Lymphoma)

New maintenance therapy for multiple myeloma looks promising, study suggests

Multiple myeloma is a form of cancer where the plasma cells in the bone marrow grow out of control, causing damage to bones as well as predisposing patients to anemia, infection and kidney failure. Unfortunately, multiple myeloma continues to progress even after a transplant. A new study now offers promising news about a new long-term therapy, lenalidomide, that can be used after transplantation to slow down the progression of the disease. (Source: ScienceDaily Headlines)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Study shows benefit of new maintenance therapy for multiple myeloma

(University of North Carolina School of Medicine) Multiple myeloma is a form of cancer where the plasma cells in the bone marrow grow out of control, causing damage to bones as well as predisposing patients to anemia, infection and kidney failure. Unfortunately, multiple myeloma continues to progress even after a transplant. A study published today in the New England Journal of Medicine offers promising news about a new long-term therapy, lenalidomide, that can be used after transplantation to slow down the progression of the disease. (Source: EurekAlert! - Cancer)

Lenalidomide Maintenance Stalls Myeloma in Trio of Clinical Trials

Lenalidomide maintenance therapy delayed recurrences significantly when given to patients newly diagnosed with multiple myeloma in a trio of clinical trials that reported much-anticipated outcomes May... (Source: OncologySTAT Latest News)

Lenalidomide for multiple myeloma: cost-effectiveness in patients with one prior therapy in England and Wales

Conclusion&nbsp;&nbsp;LEN/DEX is a cost effective oncology therapy from the perspective of the NHS for MM patients with one prior treatment. Content Type Journal ArticleCategory Original PaperPages 1-8DOI 10.1007/s10198-012-0395-6Authors Ruth E. Brown, United BioSource Corporation, 7101 Wisconsin Avenue, Suite 600, Bethesda, MD 20814, USASean Stern, United BioSource Corporation, 7101 Wisconsin Avenue, Suite 600, Bethesda, MD 20814, USASujith Dhanasiri, Celgene Ltd. (UK and Ireland), Stockley Park, Uxbridge, UKSteve Schey, King‚??s College Hospital, London, UK Journal The European Journal of Health EconomicsOnline ISSN 1618-7601Print ISSN 1618-7598 (Source: The European Journal of Health Economics)

New Drug Shows Promise for Myeloma Patients

Studies found lenalidomide lengthened time disease did not worsen, but risk of second cancers was doubled (Source: The Doctors Lounge - Oncology)

RCTs of continuous lenalidomide treatment for multiple myeloma

Source: New England Journal of Medicine (NEJM) Area: News In the New England Journal of Medicine, three double-blind, phase III, multicentre, randomised trials assess lenalidomide maintenance therapy in patients with multiple myeloma. &#160; Two studies randomised patients with stable disease after stem-cell transplantation to maintenance lenalidomide or placebo. In another study, patients who were ineligible for stem-cell transplantation received oral melphalan-prednisone- lenalidomide induction followed by randomisation to lenalidomide (MPR-R) or placebo (MPR); a third group received melphalan-prednisone (MP) and placebo. In all three studies, study-drug assignments were unblinded early after lenalidomide maintenance was shown to significantly improve progression- free survival or t...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma

Combinations of bortezomib (V) and dexamethasone (D) with either lenalidomide (R) or cyclophosphamide (C) have shown significant efficacy. This randomized phase 2 trial evaluated VDC, VDR, and VDCR in previously untreated multiple myeloma (MM). Patients received V 1.3 mg/m2 (days 1, 4, 8, 11) and D 40 mg (days 1, 8, 15), with either C 500 mg/m2 (days 1, 8) and R 15 mg (days 1-14; VDCR), R 25 mg (days 1-14; VDR), C 500 mg/m2 (days 1, 8; VDC) or C 500 mg/m2 (days 1, 8, 15; VDC-mod) in 3-week cycles (maximum 8 cycles), followed by maintenance with V 1.3 mg/m2 (days 1, 8, 15, 22) for four 6-week cycles (all arms) &ge; very good partial response was seen in 58%, 51%, 41%, and 53% (complete response rate of 25%, 24%, 22%, and 47%) of patients (VDCR, VDR, VCD, and VCD-mod, respectively); the corr...

Lenalidomide Extends Disease-Free Survival in Multiple Myeloma

(Source: Physician's First Watch current issue)

Light chain deposition disease affecting the gastrointestinal tract in the setting of post-living donor kidney transplantation.

We report a case of LCDD in living related kidney transplant recipient presenting with severe GI dysmotility, weight loss and progressive allograft dysfunction. A diagnosis of LCDD was based on the kidney biopsy findings in the failing renal allograft, along with the presence of excess serum free kappa light chains and abnormal kappa:lambda ratio. Subsequent review of GI biopsies confirmed kappa light chain immunoglobulin deposition within the stomach. Further investigation suggested additional hepatic and cardiac involvement. The patient went on to receive bortezomib, achieving a biochemical response and stabilization of his advanced renal dysfunction; however, bortezomib was discontinued due to toxicity. The patient was subsequently treated with lenalidomide and dexamethasone, which were...

Three Studies Highlighting Myeloma Treatment Advances are Featured Together in the Prestigious New England Journal of Medicine

Studies Cover REVLIMID Continuous Therapy in Newly Diagnosed Myeloma Patients and REVLIMID Maintenance Treatment Following Stem Cell Transplant (Source: International Myeloma Foundation)

Drug Delays Relapse in Multiple Myeloma (CME/CE)

(MedPage Today) -- For patients with multiple myeloma, lenalidomide (Revlimid) maintenance therapy extended the time before relapse, researchers on three clinical trials reported. (Source: MedPage Today Hematology/Oncology)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

New Drug Shows Promise for Myeloma Patients

Studies found lenalidomide lengthened time disease did not worsen, but risk of second cancers was doubled (Source: Cancercompass News: Other Cancer)

Lenalidomide shows significant benefit for myeloma patients, phase III study suggests

Medical researchers report significant time-to-progression benefit as well as survival benefit for patients who took maintenance doses of lenalidomide following stem-cell transplant. (Source: ScienceDaily Headlines)

Lenalidomide Maintenance after Stem-Cell Transplantation for Multiple Myeloma

New England Journal of Medicine, Volume 366, Issue 19, Page 1782-1791, May 2012. (Source: New England Journal of Medicine)

Lenalidomide after Stem-Cell Transplantation for Multiple Myeloma

New England Journal of Medicine, Volume 366, Issue 19, Page 1770-1781, May 2012. (Source: New England Journal of Medicine)

Continuous Lenalidomide Treatment for Newly Diagnosed Multiple Myeloma

New England Journal of Medicine, Volume 366, Issue 19, Page 1759-1769, May 2012. (Source: New England Journal of Medicine)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Lenalidomide in Myeloma ‚?? A High-Maintenance Friend

New England Journal of Medicine, Volume 366, Issue 19, Page 1836-1838, May 2012. (Source: New England Journal of Medicine)

Revlimid Delays Relapse in Multiple Myeloma (CME/CE)

(MedPage Today) -- For patients with multiple myeloma, lenalidomide (Revlimid) maintenance therapy extended the time before relapse, researchers on three clinical trials reported. (Source: MedPage Today Hematology/Oncology)

New Drug Shows Promise for Myeloma Patients

Studies found lenalidomide lengthened time disease did not worsen, but risk of second cancers was doubled Source: HealthDay Related MedlinePlus Pages: Cancer Chemotherapy, Multiple Myeloma (Source: MedlinePlus Health News)

Deferasirox treatment for myelodysplastic syndromes: ‚??real-life‚?Ě efficacy and safety in a single-institution patient population

In conclusion, the oral iron chelator deferasirox is effective and safe when used in MDS patients with transfusion requirement, also if administered concomitantly with other drugs. Content Type Journal ArticleCategory Original ArticlePages 1-5DOI 10.1007/s00277-012-1481-7Authors Massimo Breccia, Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, ItalyPaola Finsinger, Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, ItalyGiuseppina Loglisci, Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, ItalyVincenzo Federico, Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, ItalyMichelina Santopietro, Department of Cellular Biotechnologies and Hematology, Sapienza Un...

Maintenance with lenalidomide delays myeloma reappearance

NEW YORK (Reuters Health) - Lenalidomide maintenance therapy can significantly extend the time to progression and progression-free survival in patients with multiple myeloma, according to three double-blind studies in the May 10 New England Journal of Medicine. (Source: Modern Medicine)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

FDA: Revlimid Linked to Second Cancers

(MedPage Today) -- Treatment of multiple myeloma with lenalidomide (Revlimid) as maintenance therapy is associated with an increased risk of second primary cancers, the FDA warned. (Source: MedPage Today Public Health)

FDA Warning: Second Cancers Can Follow Lenalidomide in Myeloma

The Food and Drug Administration has added a warning about second-cancer risk to the label of lenalidomide, a widely used multiple myeloma drug, after a safety review lasting about 1 year.Treatment with... (Source: OncologySTAT Latest News)

FDA Drug Safety Communication: Safety review update of cancer drug Revlimid (lenalidomide) and risk of developing new types of malignancies

[5-07-2012] The U.S. Food and Drug Administration (FDA) is informing the public of an increased risk of second primary malignancies (new types of cancer) in patients with newly-diagnosed multiple myeloma who received Revlimid (lenalidomide).... (Source: Drugs.com - Pharma News)

FDA Drug Safety Communication: Increased risk of second primary malignancies in patients taking lenalidomide for multiple myeloma

Source: FDA MedWatch Area: News In April 2011, the US FDA notified the public that it would be reviewing all of the available information on the potential increased risk of second primary malignancies associated with use of lenalidomide for the treatment of multiple myeloma (MM). &#160; The FDA has completed a comprehensive review of this safety issue (see link below for details) and notes that post-marketing trials found that patients with MM treated first-line with lenalidomide had an increased risk of developing second primary malignancies compared to similar patients treated with a placebo; specifically there was an increased risk of developing acute myelogenous leukaemia, myelodysplastic syndromes, and Hodgkin's lymphoma. &#160; This safety information has been added to the d...

Revlimid (lenalidomide): Ongoing Safety Review - Increased Risk of Developing New Malignancies

Audience: Hematology, Oncology [UPDATED 05/07/2012]  FDA notified the public of an increased risk of second primary malignancies (new types of cancer) in patients with newly-diagnosed multiple myeloma who received Revlimid (lenalidomide). Clinical... (Source: Drugs.com - FDA MedWatch Alerts)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Lenalidomide: Severe neutropenia in an elderly patient: case report

(Source: Reactions)

Lenalidomide: Stevens-Johnson/toxic epidermal necrolysis overlap syndrome: case report

(Source: Reactions)

Prediction of response to therapy with ezatiostat in lower risk myelodysplastic syndrome

Conclusions: We have shown that an ezatiostat response profile contains two miRNAs that regulate expression of genes known to be implicated in MDS disease pathology. Remarkably, pathway analysis of the response profile revealed that the genes comprising the jun-N-terminal kinase/c-Jun molecular pathway, which is known to be activated by ezatiostat, are under-expressed in patients who respond and over-expressed in patients who were non-responders to the drug, suggesting that both the biology of the disease and the molecular mechanism of action of the drug are positively correlated. (Source: Journal of Hematology and Oncology)

Lenalidomide cutaneous adverse event: a case of Stevens‚??Johnson syndrome (SJS) in a primary plasma cell leukaemia patient treated with lenalidomide and dexamethasone

Content Type Journal ArticleCategory Short CommunicationPages 1-3DOI 10.1007/s00520-012-1481-0Authors A. Siniscalchi, Department of Hematology, S. Eugenio Hospital, ‚??Tor Vergata‚?Ě University, Piazzale dell‚??Umanesimo, 10, 00100 Rome, ItalyA. Tendas, Department of Hematology, S. Eugenio Hospital, ‚??Tor Vergata‚?Ě University, Piazzale dell‚??Umanesimo, 10, 00100 Rome, ItalyL. Morino, Department of Hematology, S. Eugenio Hospital, ‚??Tor Vergata‚?Ě University, Piazzale dell‚??Umanesimo, 10, 00100 Rome, ItalyT. Dentamaro, Department of Hematology, S. Eugenio Hospital, ‚??Tor Vergata‚?Ě University, Piazzale dell‚??Umanesimo, 10, 00100 Rome, ItalyA. De Bellis, Department of Plastic, Reconstructive and Aesthetic Surgery, S. Eugenio Hospital, Rome, ItalyA. Perrotti, Department of Hematolo...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide

Authors: A Lopez-Girona, D Mendy, T Ito, K Miller, A K Gandhi, J Kang, S Karasawa, G Carmel, P Jackson, M Abbasian, A Mahmoudi, B Cathers, E Rychak, S Gaidarova, R Chen, P H Schafer, H Handa, T O Daniel, J F Evans & R Chopra (Source: Leukemia)

Clinical experience with thalidomide and lenalidomide in multiple myeloma.

Authors: Moehler T Abstract Thal has antiangiogenic and immunomodulatory activity. Clinical research provided clear evidence that Thal belongs to the most active drugs for the treatment of multiple myeloma e.g. leading to decrease of monoclonal protein of at least 50 % in 30 % of patients with relapsed or refractory multiple myeloma. Randomized trials that were designed based on a large body of evidence from phase II trials determined that Thal significantly increases total response rate, progression-free and in some studies overall survival in combination regimens (dexamethason and or chemotherapy) for relapsed as well as newly diagnosed patients and was therefore approved for first-line treatment of Multiple Myeloma. Strict guidelines apply due to the teratogenic effects of Thal ...

Phase 1 dose-ranging study of ezatiostat hydrochloride in combination with lenalidomide in patients with non-deletion (5q) low to intermediate-1 risk myelodysplastic syndrome (MDS)

Conclusions: The tolerability and activity profile of ezatiostat co-administered with lenalidomide supportsthe further development of ezatiostat in combination with lenalidomide in MDS and alsoencourages studies of this combination in other hematologic malignancies wherelenalidomide is active.Trial registrationClinicaltrials.gov: NCT01062152 (Source: Journal of Hematology and Oncology)

Lenalidomide, Cyclophosphamide and Dexamethasone (CRd) for Light Chain Amyloidosis: Long Term Results From a Phase 2 Trial

In this phase II study of patients with light-chain amyloidosis, half of whom had stage III cardiac disease, lenalidomide, cyclophosphamide, and dexamethasone produced durable responses with manageable... (Source: OncologySTAT Journal Scans)

Halofuginone inhibits multiple myeloma growth in vitro and in vivo and enhances cytotoxicity of conventional and novel agents

This study demonstrated the anti‚?źtumour activity of HF against a panel of human MM cell lines and primary patient‚?źderived MM cells, regardless of their sensitivity to conventional therapy or novel agents. HF showed anti‚?źMM activity in vivo using a myeloma xenograft mouse model. HF suppressed proliferation of myeloma cells alone and when co‚?źcultured with bone marrow stromal cells. Similarly, HF induced apoptosis in MM cells even in the presence of insulin‚?źlike growth factor 1 or interleukin 6. Importantly, HF, even at high doses, did not induce cytotoxicity against CD40 activated peripheral blood mononuclear cells from normal donors. HF treatment induced accumulation of cells in the G0/G1 cell cycle and induction of apoptotic cell death associated with depletion of mitochondrial m...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Lenalidomide in multiple myeloma: Current status and future potential

AbstractThe clinical development of lenalidomide (Revlimid‚?Ę), then pomalidomide (Actimid‚?Ę) as members of immunomodulatory drugs (IMiDs) for the treatment of multiple myeloma (MM), exemplifies how insight into disease biology can lead to design of effective therapeutic agents. Increased experience and understanding of IMiD's diverse biological effects has lead to rational design of lenalidomide‚?źbased treatment‚?źregimens over recent years. However, much about lenalidomide is yet to be understood and fully exploited. Here, we review what is known of of lenalidomide's biological effects, clinical certainties and uncertainties in the treatment of MM, and explore its future potential with other synergistic therapeutic agents. Am. J. Hematol., 2012. ¬© 2012 Wiley Periodicals, Inc. (Source:...

Lenalidomide enhancement of human T‚?źcell functions in HIV‚?źinfected and HIV‚?źnegative CD4 T lymphocytopenic patients

SummarySuppressed T‚?źcell functions in HIV infection were identified and corrected by lenalidomide in middle‚?źaged HIV‚?źinfected patients. Chemotaxis of T‚?źcells from HIV‚?źinfected men (n=6,mean43 years) to sphingosine 1‚?źphosphate (S1P) and CCL21 was significantly lower than that of HIV‚?źnegative men (n=6,mean 41 years) and was enhanced significantly up to control levels by 100 and 1,000 nM lenalidomide. Generation of IL‚?ź2, but not IFN‚?źő≥, by T‚?źcells of middle‚?źaged HIV‚?źinfected men was significantly lower than that for controls and was increased significantly by 10 to 1,000 nM lenalidomide up to a maximum of over 300%. CD4 and CD8 T‚?źcells isolated from healthy middle‚?źaged men and reconstituted in vitro at a low CD4:CD8 ratio typical of HIV infection had depressed chem...

Itraconazole/lenalidomide interaction: Febrile neutropenia and neutropenia-related infections: case report

(Source: Reactions)

Short-term Lenalidomide (Revlimid) Administration Ameliorates Cardiomyocyte Contractile Dysfunction in ob/ob Obese Mice.

This study was designed to examine the effect of lenalidomide on cardiac contractile function in ob/ob obese mice. C57BL lean and ob/ob obese mice were given lenalidomide (50‚??mg/kg/d, p.o.) for 3 days. Body fat composition was assessed by dual energy X-ray absorptiometry. Cardiomyocyte contractile and intracellular Ca(2+) properties were evaluated. Expression of TNF-őĪ, IL-6, Fas, Fas ligand (FasL), the short-chain fatty acid receptor GPR41, the NF–?B regulator I–?B, ER stress, the apoptotic protein markers Bax, Bcl-2, Caspase-8, tBid, cytosolic cytochrome C and Caspase-12, and the stress signaling molecules p38 and ERK were evaluated by western blot. ob/ob mice displayed elevated serum TNF-őĪ and IL-6 levels, fat composition and glucose intolerance, the effects of which except glucose i...

REVLIMID (Lenalidomide) Capsule [Celgene Corporation]

Updated Date: Apr 20, 2012 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

PSA Response to Lenalidomide Therapy in a Pre-Treated Patient with Metastatic Prostate Cancer Refractory to Hormones and Chemotherapy: A Case Report

Case Rep Oncol 2012;5:181‚??186 (DOI:10.1159/000336481) (Source: Karger Publishers)

Waldenström Macroglobulinemia: 2012 update on diagnosis, risk stratification, and management

AbstractDisease Overview: Waldenstr√∂m macroglobulinemia (WM) is a lymphoplasmacytic lymphoma with immunoglobulin M (IgM) monoclonal protein. Clinical features include anemia, thrombocytopenia, hepatosplenomegaly, and lymphadenopathy.Diagnosis: Presence of IgM monoclonal protein associated with ‚?•10% clonal lymphoplasmacytic cells in bone marrow confirms the diagnosis.Risk Stratification: Age, hemoglobin level, platelet count, ő≤2 microglobulin, and monoclonal IgM concentrations are characteristics required for prognosis.Risk‚?źAdapted Therapy: Not all patients who fulfill WM criteria require therapy; these patients can be observed until symptoms develop. Rituximab‚?źbased therapy is used in virtually all US patients with WM and can be combined with alkylating agent or purine nucleoside a...

Myelodysplasia-associated immunophenotypic alterations of bone marrow cells in myeloma: are they present at diagnosis or are they induced by lenalidomide?

Authors: Matarraz S, Paiva B, Diez-Campelo M, Lopez-Corral L, Perez E, Mateos MV, Giraldo P, Hernandez MT, San-Miguel JF, Orfao A Abstract Increased risk of acute myeloid leukemia/myelodysplastic syndromes following treatment has been reported in multiple myeloma, but whether dysplastic features are already present at diagnosis remains to be investigated. Using multiparameter flow cytometry, we analyzed the distribution and phenotype of bone marrow hematopoietic cells from 47 multiple myeloma patients (15 symptomatic and 32 high-risk smoldering). From the 32 smoldering myeloma patients, 18 were studied at baseline and 22 after nine cycles of Lenalidomide/Dexamethasone treatment following the QUIREDEX trial (including eight from baseline). Phenotypic alterations of bone marrow cells...

[AL amyloidosis].

Authors: Gadó K, Domján G Abstract AL amyloidosis is a systemic disease characterised by pathogenetic proteins produced by malignant plasma cells and the deposition of them in different organs of the body. Amyloidogenic protein is the light chain of the monoclonal immunoglobulin, which becomes water insoluble, precipitates and deposites in the extracellular space resulting damage of organ function. AL amyloidosis belongs to plasma cell dyscrasias or it can associate to other monoclonal B-cell diseases. Diagnosis - such as in case of other types of amyloidosis - is based on histology. Identification of the amyloidogenic protein often needs special examinations. The goal of the therapy is the eradication of the malignant cell clone. Therapeutical armamentarium has been largely flar...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Compartment-specific bioluminescence imaging platform for the high-throughput evaluation of antitumor immune function

This study provides a framework to identify novel immunomodulatory agents and to prioritize compounds for clinical development on the basis of their effect on antitumor immunity. (Source: Blood)

Efficacy of lenalidomide plus dexamethasone for POEMS syndrome relapsed after autologous peripheral stem‚?źcell transplantation

(Source: American Journal of Hematology)

Growth factor plus preemptive (‚??just-in-time‚??) plerixafor successfully mobilizes hematopoietic stem cells in multiple myeloma patients despite prior lenalidomide exposure

Growth factor plus preemptive (&#8216;just-in-time&#8217;) plerixafor successfully mobilizes hematopoietic stem cells in multiple myeloma patients despite prior lenalidomide exposure Bone Marrow Transplantation advance online publication, April 9, 2012. doi:10.1038/bmt.2012.60 Authors: L J Costa, J Abbas, K R Hogan, C Kramer, K McDonald, C D Butcher, A Littleton, K Shoptaw, Y Kang & R K Stuart (Source: Bone Marrow Transplantation)

SIE, SIES, GITMO evidence-based guidelines on novel agents (thalidomide, bortezomib, and lenalidomide) in the treatment of multiple myeloma

Abstract&nbsp;&nbsp;In this project, we produced drug-specific recommendations targeting the use of new agents for multiple myeloma (MM). We used the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) system which separates the judgments on quality of evidence from the judgment about strength of recommendations. We recommended thalidomide and bortezomib in MM patients candidates to autologous stem cell transplantation (ASCT) (weak positive). We did not recommend novel agents as maintenance therapy after ASCT (weak negative). In patients not candidate to ASCT, thalidomide or bortezomib (strong positive) associated with melphalan and prednisone were recommended. In these patients, no specific course of action could be recommended as for maintenance therapy. In pa...

Novel and Emerging Drugs for Acute Myeloid Leukemia.

Authors: Stein EM, Tallman MS Abstract Acute myeloid leukemia (AML) is a challenging disease to treat with the majority of patients dying from their illness. While overall survival has been markedly prolonged in acute promyelocytic leukemia (APL), survival in younger adults with other subtypes of AML have only modestly improved over the last twenty years. Physicians who treat AML eagerly await drugs like Imatinib for chronic myeloid leukemia, Cladribine for hairy cell leukemia, and Rituximab for non-Hodgkin Lymphoma which have had an important impact on improving outcome. Recent research efforts have focused on refining traditional chemotherapeutic agents to make them more active in AML, targeting specific genetic mutations in myeloid leukemia cells, and utilizing novel agents such...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Therapy with lenalidomide plus dexamethasone-induced bone formation in a patient with refractory multiple myeloma.

We report a case of refractory multiple myeloma that was treated with lenalidomide combined with dexamethasone (RD regimen). As a result, the patient's myeloma protein expression was markedly reduced, and her hematological profile was improved. However, the treatment also induced tetany by reducing her serum calcium and magnesium levels and elevating her alkaline phosphatase levels. In addition, conventional radiography and computed tomography detected osteosclerosis. These findings suggest that the RD regimen affects bone formation, possibly by activating osteoblasts. This is to our knowledge the first report to suggest that lenalidomide, an immunomodulatory drug, affects osteogenesis, at least in a certain subpopulation of patients with multiple myeloma. PMID: 22467268 [PubMed - as s...

IMWG consensus on maintenance therapy in multiple myeloma

Maintaining results of successful induction therapy is an important goal in multiple myeloma. Here, members of the International Myeloma Working Group review the relevant data. Thalidomide maintenance therapy after autologous stem cell transplantation improved the quality of response and increased progression-free survival (PFS) significantly in all 6 studies and overall survival (OS) in 3 of them. In elderly patients, 2 trials showed a significant prolongation of PFS, but no improvement in OS. A meta-analysis revealed a significant risk reduction for PFS/event-free survival and death. The role of thalidomide maintenance after melphalan, prednisone, and thalidomide is not well established. Two trials with lenalidomide maintenance treatment after autologous stem cell transplantation and one...

Lenalidomide plus donor-lymphocytes infusion after allogeneic stem-cell transplantation with reduced-intensity conditioning in patients with high-risk multiple myeloma

Myeloma relapse is the main cause of death after allogeneic stem cell transplantation. The aim of our observational study was to evaluate the anti-myeloma effect of lenalidomide followed by donor-lymphocyte infusion (DLI) as post-transplantation adoptive immunotherapy. Twelve patients with refractory myeloma were analyzed. The median age at transplantation was 56 years (range, 46‚??64 years). All patients received reduced-intensity conditioning. Patients were included if progressive or residual disease was observed at day +100 and if no signs of graft-vs-host disease were evident. DLIs were administered after two cycles of lenalidomide. Median dose of lenalidomide was 15 mg (range, 10‚??25 mg). Patients received a median of six cycles (range, 1‚??10 cycles). Nine patients (60%) received an...

Second malignancies after multiple myeloma: from 1960s to 2010s

Based on small numbers, recent reports from 3 randomized trials have consistently demonstrated more hematologic malignancies in patients treated with lenalidomide as maintenance (vs placebo). This fact has prompted concern and highlighted the association between multiple myeloma and second malignancies. Furthermore, an excess of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) after multiple myeloma has been known for over 4 decades. Most prior studies have been restricted because of small numbers of patients, inadequate follow-up, and limitations of ascertainment of second malignancies. Although the underlying biologic mechanisms of AML/MDS after multiple myeloma are unknown, treatment-related factors are presumed to be responsible. Recently, an excess risk of AML/MDS was ...

A review of second primary malignancy in patients with relapsed or refractory multiple myeloma treated with lenalidomide

In a retrospective pooled analysis of 11 clinical trials of lenalidomide-based therapy for relapsed/refractory multiple myeloma (MM; N = 3846), the overall incidence rate (IR, events per 100 patient-years) of second primary malignancies (SPMs) was 3.62. IR of invasive (hematologic and solid tumor) SPMs was 2.08, consistent with the background incidence of developing cancer. In a separate analysis of pooled data from pivotal phase 3 trials of relapsed or refractory MM (N = 703), the overall IR of SPMs was 3.98 (95% confidence interval [CI], 2.51-6.31) with lenalidomide/dexamethasone and 1.38 (95% CI, 0.44-4.27) with placebo/dexamethasone; IRs of nonmelanoma skin cancers were 2.40 (95% CI, 1.33-4.33) and 0.91 (95% CI, 0.23-3.66), respectively; IRs of invasive SPMs were 1.71 (95% CI, 0.86-3.4...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Plasma exchange and rituximab treatment for lenalidomide-associated cold agglutinin disease.

CONCLUSION: In addition to warm AIHA, lenalidomide use can also be associated with development of CAD. Rituximab given in conjunction with plasma exchange can be effective in treating CAD in this setting. PMID: 22435421 [PubMed - as supplied by publisher] (Source: Transfusion)

Co-existing chronic myeloid leukaemia and multiple myeloma: rapid response to lenalidomide during imatinib treatment.

Authors: Offiah C, Quinn JP, Thornton P, Murphy PT PMID: 22426625 [PubMed - as supplied by publisher] (Source: International Journal of Hematology)

Effect of a patient support program on access to oral therapy for hematologic malignancies.

CONCLUSION: The percentage of patients who were dispensed prescriptions for lenalidomide or thalidomide did not differ significantly between those who were enrolled in a patient assistance program and those who were not. The median time between prescription authorization and first dispensing was comparable among program and nonprogram patients. PMID: 22382483 [PubMed - in process] (Source: American Journal of Health-System Pharmacy : AJHP)

Celgene Contracts with TNH Pharmacy II as a RevAssist Program Pharmacy...

TNH Pharmacy II, a specialty pharmacy, adds REVLIMID to its growing list of limited distribution drug contract agreements. State-of-the-art systems generate enthusiasm for TNH as Oncology Pharmacy.(PRWeb March 13, 2012)Read the full story at http://www.prweb.com/releases/2012/3/prweb9263276.htm (Source: PRWeb: Medical Pharmaceuticals)

Lenalidomide: Febrile reactions in elderly patients: 3 case reports

(Source: Reactions)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Dexamethasone/lenalidomide: Cerebral venous thrombosis in an elderly patient: case report

(Source: Reactions)

Growth Differentiation Factor 15 in Multiple Myeloma

In this study, we report that GDF15 significantly increases survival of stroma-dependent multiple myeloma cells including primary multiple myeloma cells. In particular, GDF15 conferred resistance to melphalan, bortezomib, and to a lesser extent, lenalidomide in both stroma-dependent and stroma-independent multiple myeloma cells. Akt-dependent signaling was critical to mediate the effects of GDF15, whereas Src and extracellular signal-regulated kinase 1/2 signaling pathways were not involved. Given these results, we tested the clinical significance of plasma concentrations of GDF15 (pGDF15) in 131 patients with multiple myeloma and found that it correlated with disease prognosis. Specifically, patients with high levels of pGDF15 had lower probabilities of event-free and overall survival 30 ...

Efficacy of lenalidomide plus dexamethasone for POEMS syndrome relapsed after autologous peripheral stem cell transplantation

(Source: American Journal of Hematology)

Efficacy of lenalidomide plus dexamethasone for POEMS syndrome relapsed after autologous peripheral stem‚?źcell transplantation

(Source: American Journal of Hematology)

Concomitant Waldenstrom macroglobulinemia and IgA plasmablastic myeloma in a patient with untreated IgM paraproteinemia: sequential development of biclonal B-cell neoplasms over a 10-year period in a single individual

We report the first case of sequential development of Waldenstrom macroglobulinemia and plasma cell myeloma over a 10-year period in a 73-year-old man with untreated IgM paraproteinemia. The bone marrow biopsy demonstrated dual populations of lymphoid cells: small mature lymphocytes and immature plasma cells. Although both Waldenstrom macroglobulinemia and plasma cell myeloma were restricted to őļ light chain, plasma cell myeloma expressed IgA, whereas the plasmacytic component in Waldenstrom macroglobulinemia produced IgM. The biclonal nature of these 2 B-cell neoplasms was further supported by immunofixation electrophoresis and cytogenetic studies. Although the clinical outcome of plasma cell myeloma when concomitant with other indolent B-cell neoplasms is unfavorable, our patient seemed...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

The potential benefits of participating in early‚?źphase clinical trials in multiple myeloma: long‚?źterm remission in a patient with relapsed multiple myeloma treated with 90 cycles of lenalidomide and bortezomib

We present the case of a woman with relapsed multiple myeloma (MM) who received combination lenalidomide and bortezomib therapy for 90 cycles followed by continuous lenalidomide monotherapy and has completed over 100 cycles of treatment to date. The patient was diagnosed with advanced‚?źstage, symptomatic MM in 2001. Following a partial response (PR) to dexamethasone in combination with pamidronate and thalidomide, the patient underwent protocol‚?źdirected non‚?źmyeloablative allogeneic bone marrow transplantation from her matched sibling donor the following year. In 2004, the patient relapsed and was enrolled in a phase I, dose‚?źescalation trial of lenalidomide plus bortezomib for relapsed and refractory MM. After eight cycles of study treatment, the patient achieved a minimal response. ...

Cytogenetic and molecular predictors of response in patients with myeloid malignancies without del[5q] treated with lenalidomide

Conclusions: Normal karyotype and gain of chromosome 8 material was predictive of response to LEN in non-del[5q] patients with myeloid malignancies. (Source: Journal of Hematology and Oncology)

In vivo efficacy of the diuretic agent ethacrynic acid against multiple myeloma

This study investigated the antitumor effect of EA in vivo in a murine myeloma model. In vivo, tumor growth was significantly reduced and overall survival significantly prolonged in mice treated with EA as compared to untreated mice. Interestingly, this effect was higher as compared to the effect by lenalidomide, a commonly used drug against myeloma. These results reveal a significant in vivo effect by EA against myeloma. (Source: Leukemia Research)

Pachymeningeal involvement in POEMS syndrome: Dramatic cerebral MRI improvement after lenalidomide therapy

(Source: American Journal of Hematology)

NHS Evidence Update (February 2012) of NICE guideline on reducing risk of venous thromboembolism in patients admitted to hospital

Source: NHS Evidence Area: News NHS Evidence has issued a summary of selected new evidence relevant to NICE clinical guideline 92 (published 2010) on reducing the risk of venous thromboembolism (VTE) in patients admitted to hospital. &#160; The following key messages have been highlighted which could result in a potential change in guidance: &#160; .&#160;Evidence appears to confirm that thalidomide in patients with multiple myeloma may increase the risk of VTE, and evidence now also suggests an elevated risk with lenalidomide in this population. &#160; .&#160;A NICE technology appraisal has recently recommended apixaban as an option for the prevention of VTE following elective total hip and knee replacement. (Source: NeLM - News)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Potent in vitro and in vivo activity of an Fc-engineered humanized anti-HM1.24 antibody against multiple myeloma via augmented effector function

In this study, we investigated in vitro and in vivo anti-MM activities of XmAb5592, a humanized anti-HM1.24 mAb with Fc-domain engineered to significantly enhance FcR binding and associated immune effector functions. XmAb5592 increased antibody-dependent cellular cytotoxicity (ADCC) several fold relative to the anti-HM1.24 IgG1 analog against both MM cell lines and primary patient myeloma cells. XmAb5592 also augmented antibody dependent cellular phagocytosis (ADCP) by macrophages. Natural killer (NK) cells became more activated by XmAb5592 than the IgG1 analog, evidenced by increased cell surface expression of granzyme B&ndash;dependent CD107a and MM cell lysis, even in the presence of bone marrow stromal cells. XmAb5592 potently inhibited tumor growth in mice bearing human MM xenografts ...

Pulmonary Zygomycosis in a Non-neutropenic Patient with Myelodysplastic Syndrome on Lenalidomide.

We report a case of a 75-year-old man with myelodysplastic syndrome (MDS) treated with lenalidomide for three months who developed respiratory failure and a rapidly progressive left upper lobe consolidation. An extensive work up was unrevealing of the etiology and the patient expired. A full autopsy was declined, but an in situ post-mortem transbronchial lung biopsy revealed pulmonary zygomycosis. This unique case illustrates the potential risks of lenalidomide therapy in patients with MDS and the difficulties in diagnosing pulmonary zygomycosis. To our knowledge this is the first report of a diagnostic in situ post-mortem transbronchial lung biopsy. PMID: 22369887 [PubMed - as supplied by publisher] (Source: Respiratory Care)

Onyx completes patient enrollment in ASPIRE trial

Onyx Pharmaceuticals has completed patient enrolment in the Carfilzomib, Lenalidomide and DexamethaSone versus Lenalidomide and Dexamethasone for the treatment of PatIents with Relapsed Multiple MyEloma (ASPIRE) trial. (Source: Drug Development Technology)

A phase 2 study of pegylated liposomal doxorubicin, bortezomib, dexamethasone and lenalidomide for patients with relapsed/refractory multiple myeloma

A phase 2 study of pegylated liposomal doxorubicin, bortezomib, dexamethasone and lenalidomide for patients with relapsed&#47;refractory multiple myeloma Leukemia advance online publication, February 22, 2012. doi:10.1038/leu.2012.51 Authors: J R Berenson, O Yellin, T Kazamel, J D Hilger, C-S Chen, A Cartmell, T Woliver, M Flam, E Bravin, Y Nassir, R Vescio & R A Swift (Source: Leukemia)

Latest advances and current challenges in the treatment of multiple myeloma

Authors: Anuj Mahindra, Jacob Laubach, Noopur Raje, Nikhil Munshi, Paul G. Richardson & Kenneth Anderson Effectively treating patients with multiple myeloma is challenging. The development of therapeutic regimens over the past decade that incorporate the proteasome inhibitor bortezomib and the immunomodulatory drugs thalidomide and lenalidomide has been the cornerstone of improving the outcome of patients with myeloma. Although these treatment (Source: Nature Clinical Practice Oncology)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Aspirin, LMWH prevent VTE in patients treated for multiple myeloma

Thromboprophylaxis with either aspirin or low molecular weight heparin is associated with a low incidence of venous thromboembolism among patients with newly diagnosed multiple myeloma receiving lenalidomide-based treatment, Italian researchers report. (Source: MedWire News - Thrombosis)

Novel therapeutic agents for the management of multiple myeloma patients with renal impairment.

CONCLUSIONS: PMID: 22328563 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Vaccine response augmented by lenalidomide in multiple myeloma

Noonan K. Clin Cancer Res. 2012;doi:10.1158/1078-0432.CCR-11-1221. (Source: HemOncToday.com)

NHS Evidence Update: Reducing the risk of VTE

Source: NHS Evidence Area: News This latest update identifies new evidence relevant AND SUBSEQUENT TO to NICE clinical guideline 92 'Reducing the risk of venous thromboembolism (VTE) in patients admitted to hospital' (published 2010) that might generate future change to the practice laid out in the guidance. &#160; Key messages pertaining to newly published evidence include the following: &#160; .&#160;Evidence appears to confirm that thalidomide in patients with multiple myeloma (MM) may increase the risk of venous thromboembolism (VTE), and evidence now also suggests an elevated risk with lenalidomide in this population. &#160; . The most effective thromboprophylaxis in patients receiving thalidomide or lenalidomide for MM does not yet appear to have been established by curr...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Pachymeningeal involvement in POEMS syndrome: Dramatic cerebral MRI improvement after lenalidomide therapy

AbstractPOEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes) syndrome is a rare multisystemic disease associated with plasma cell dyscrasia and increased serum or plasma Vascular Endothelial Growth Factor (VEGF) levels, the latter likely responsible for several POEMS syndrome manifestations. Whereas peripheral neuropathy is the main neurological feature and a mandatory diagnostic criterium, central nervous system involvement is less common except for papilledema and stroke. We recently reported the frequent occurrence at brain MRI of cranial pachymeningeal involvement in a series of POEMS syndrome patients. Meningeal histopathology revealed hyperplasia of meningothelial cells, neovascularisation and obstructive vessel remodelling without inflammatory si...

Lenalidomide/pamidronic acid/zoledronic acid: Osteonecrosis of the jaw (first report with lenalidomide) in an elderly patient: case report

(Source: Reactions)

[News] Analysis affirms secondary cancer risk with lenalidomide

An increased risk of a secondary malignancy in patients taking the immunomodulatory drugs lenalidomide and thalidomide has again been reported, in a retrospective pooled analysis of nine European trials that included patients with newly diagnosed multiple myeloma. (Source: The Lancet Oncology)

Efficacy of bortezomib, lenalidomide and dexamethasone (VRD) in secondary plasma cell leukaemia

(Source: British Journal of Haematology)

The potential benefits of participating in early‚?źphase clinical trials in multiple myeloma: long‚?źterm remission in a patient with relapsed multiple myeloma treated with 90 cycles of lenalidomide and bortezomib

We present the case of a woman with relapsed multiple myeloma (MM) who received combination lenalidomide and bortezomib treatment for 90 cycles followed by continuous lenalidomide monotherapy and has completed over 100 cycles of treatment to date. The patient was diagnosed with advanced stage, symptomatic MM in 2001. Following a partial response (PR) to dexamethasone in combination with pamidronate and thalidomide, the patient underwent protocol‚?źdirected non‚?źmyeloablative allogeneic bone marrow transplantation from her matched sibling donor the following year. In 2004, the patient relapsed and was enrolled in a phase I, dose escalation trial of lenalidomide plus bortezomib for relapsed and refractory MM. After 8 cycles of study treatment, the patient achieved a minimal response. The pa...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Efficacy of bortezomib, lenalidomide and dexamethasone (VRD) in secondary plasma cell leukaemia

(Source: British Journal of Haematology)

Lenalidomide plus dexamethasone a winner as second-line therapy

(Source: PharmacoEconomics and Outcomes News)

The 39th David A. Karnofsky Lecture: Bench-to-Bedside Translation of Targeted Therapies in Multiple Myeloma [SPECIAL ARTICLE]

Multiple myeloma (MM) is a remarkable example of rapid bench-to-bedside translation in new drug development. The proteasome inhibitor bortezomib and immunomodulatory drug lenalidomide targeted MM cells in the bone marrow (BM) microenvironment to overcome conventional drug resistance in laboratory and animal models and were rapidly translated into clinical trials demonstrating their efficacy in patients with relapsed and then newly diagnosed MM, with a doubling of the median survival as a direct result. The future is even brighter. First, immune-based therapies are being developed (eg, elotuzumab monoclonal antibody [MoAb]; CD138DM immunotoxin; MM cell&ndash;dendritic cell vaccines; CD138, CS-1, and XBP-1 peptide vaccines; anti-17 MoAb; and other treatments to overcome causes of immune dysf...

p53 Nuclear Expression Correlates With Hemizygous TP53 Deletion and Predicts an Adverse Outcome for Patients With Relapsed/Refractory Multiple Myeloma Treated With Lenalidomide.

Authors: Chen MH, Qi CX, Saha MN, Chang H Abstract del(17p13)(TP53) seems to be an independent poor prognostic factor in patients with relapsed/refractory multiple myeloma (MM) receiving lenalidomide. However, whether aberrant p53 nuclear expression detected by immunohistochemical analysis can be used as a surrogate marker for del(17p13)(TP53) in prognostic evaluation of lenalidomide-treated relapsed/refractory MM remains unclear. The p53 expression in myeloma cells from 88 patients was evaluated by immunohistochemical analysis, and 17p13(TP53) gene status was examined by fluorescence in situ hybridization (FISH). FISH detected hemizygous del(17p13)(TP53) in 13 (15%), and immunohistochemical analysis detected p53 nuclear expression in 11 cases (13%). del(17p13) (TP53) and p53 expre...

Aspirin or enoxaparin thromboprophylaxis for patients with newly diagnosed multiple myeloma treated with lenalidomide

This study was registered at www.clinicaltrials.gov as #NCT00551928. (Source: Blood)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Management of Myeloproliferative Neoplasms: From Academic Guidelines to Clinical Practice

Abstract&nbsp;&nbsp;Myeloproliferative neoplasms (MPNs) are clonal disorders characterized by excessive production of mature cells. In most of the classic Philadelphia-negative MPNs‚??polycythemia vera (PV), essential thrombocythemia (ET), and MPN-associated myelofibrosis (MPN-MF)‚??oncogenic mutations affecting JAK2 or MPL lead to constitutive activation of cytokine-regulated intracellular signalling pathways. The traditional therapy for PV and ET is the prevention of thrombotic events with antiproliferative agents in association with aspirin. New drugs such as pegylated interferon and anti-JAK agents are candidates for slowing the evolution to myelofibrosis or leukemia. Conventional therapy for MPN-MF is driven by clinical needs, primarily anemia and splenomegaly. Lenalidomide and ...

Evidence Does Not Support Clinically Significant Lenalidomide-CCI-779 Interaction via P-Glycoprotein [CORRESPONDENCE]

(Source: Journal of Clinical Oncology)

REVLIMID (Lenalidomide) Capsule [Celgene Corporation]

Updated Date: Jan 18, 2012 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

Immunoglobulin light chain amyloidosis: 2012 update on diagnosis, prognosis, and treatment

AbstractDisease Overview: Immunoglobulin (Ig) light chain amyloidosis is a clonal but nonproliferative plasma cell disorder in which fragments of an Ig light chain are deposited in tissues. The clinical features depend on the organs involved but can include restrictive cardiomyopathy, nephrotic syndrome, hepatic failure, and peripheral/autonomic neuropathy.Diagnosis: Tissue biopsy stained with Congo red demonstrating amyloid deposits with apple‚?źgreen birefringence is required for diagnosis. Invasive organ biopsy is not required because amyloid deposits can be found in bone marrow biopsy or subcutaneous fat aspirate in 85% of patients. Prognosis: N‚?źterminal pro‚??brain natriuretic peptide and serum troponin T values are used to classify patients into three groups of approximately equal ...

Lenalidomide: Neutropenia and thrombocytopenia in elderly patients: 3 case reports

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Intermediate-Dose versus Low-Dose Cyclophosphamide and Granulocyte Colony-Stimulating Factor for Peripheral Blood Stem Cell Mobilization in Patients with Multiple Myeloma Treated with Novel Induction Therapies

In conclusion, compared with LD-CY, ID-CY produced a more robust peripheral blood progenitor cell mobilization and significantly reduced the rates of mobilization failure. These data caution against the use of LD-CY‚??containing mobilization strategies in patients with multiple myeloma undergoing stem cell collection after novel induction regimens. (Source: Biology of Blood and Marrow Transplantation)

Retrospective analysis affirms secondary cancer risk with lenalidomide

Source: Lancet Oncology Area: News The Lancet Oncology has featured a news article discussing research presented at the annual meeting of the American Society of Hematology (ASH), which reports an increased risk of secondary malignancy in association with use of lenalidomide and thalidomide. &#160; Researchers presented the results of a retrospective pooled analysis of nine trials of the European Myeloma Network, in which 38 solid tumours and 10 haematological malignancies were reported in 2,283 patients (2.1%) with newly diagnosed multiple myeloma who were followed up for four years.&#160; The incidences were 0.95 cases per 100 people per year for lenalidomide maintenance after high-dose melphalan and 1.05 cases per 100 people per year for melphalan and thalidomide.&#160; These rates...

Lenalidomide-Induced Immunomodulation in Multiple Myeloma: Impact on Vaccines and Antitumor Responses.

CONCLUSIONS: This is the first clinical evidence demonstrating that lenalidomide augments vaccine responses and endogenous antitumor immunity in patients and as such may serve as an adjuvant for cancer and possibly infectious vaccines. PMID: 22241792 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Lenalidomide alone or lenalidomide plus dexamethasone significantly inhibit IgG and IgM in vitro‚?¶A possible explanation for their mechanism of action in treating multiple myeloma.

Authors: Shannon E, Sandoval F, Greig N, Stagg P Abstract Lenalidomide (len) is an analog of thalidomide (thal), and both are used in the treatment of a diverse group of medical conditions. A common finding in this group is the detection of immunoglobulin in skin lesions, or high levels of immunoglobulin or myeloma protein in serum and urine. While their mechanism(s) of action is not known, the drugs are noted for their ability to modulate monocyte, lymphocyte, and natural killer cell functions; suppression of immunoglobulin synthesis could offer an explanation for their effectiveness in treating multiple myeloma (MM). Our objective was to determine if, on an equimolar basis, thal, len or dexamethasone (dex) could affect pokeweed (PWM)-induced synthesis of IgG, IgM and IL-2. When p...

Immune Reconstitution in Chronic Lymphocytic Leukemia

This article reviews the immune defect in CLL and discusses strategies aimed at repairing or circumventing this defect. In particular, it focuses on recent developments in the areas of CD40 ligand (CD40L/CD154) gene therapy, immunomodulatory agents such as lenalidomide, and adoptive transfer of T cells bearing chimeric antigen receptors. Content Type Journal ArticleCategory Chronic Lymphocytic Leukemia (S O'Brien, Section Editor)Pages 1-8DOI 10.1007/s11899-011-0106-xAuthors John C. Riches, Barts Cancer Institute, Queen Mary University of London, 3rd Floor John Vane Science Centre, Charterhouse Square, London, EC1M 6BQ UKAlan G. Ramsay, Barts Cancer Institute, Queen Mary University of London, 3rd Floor John Vane Science Centre, Charterhouse Square, London, EC1M 6BQ UKJohn G. Gribbe...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Combination strategies in myelodysplastic syndromes.

Authors: Ornstein MC, Sekeres MA Abstract The myelodysplastic syndromes (MDS) consist of an array of clonal hematological malignancies resulting from disorders of pluripotent hematopoietic stem cells. MDS is associated with a poor overall prognosis and patients are categorized as higher risk and lower risk on the basis of the International Prognostic Scoring System. Currently, lenalidomide, azacitidine, and decitabine are the only three FDA-approved drugs for MDS. Traditional therapies for MDS involve the administration of single agents providing either supportive measures or disease-modifying effects directed to slowing progression to acute myeloid leukemia (AML) and improving survival. Recently, however, there has been increasing evidence suggesting that the combination of drugs ...

Interstitial pneumonitis associated with the immunomodulatory drugs thalidomide and lenalidomide.

Authors: Iino M PMID: 22198829 [PubMed - as supplied by publisher] (Source: International Journal of Hematology)

Hematologic malignancies and thrombosis

Abstract: Patients with hematologic malignancies have an increased risk of venous thromboembolism (VTE), particularly at diagnosis and during the treatment with chemotherapy, asparaginase or immunomodulatory drugs (IMiDs). A disease-dependent hypercoagulable condition associated with other risk factors like drugs, central venous catheter (CVC), immobility and infections are responsible for this high VTE rate. Thrombotic complications have a significant impact on morbidity and in some cases also on mortality of patients with onco-hematologic diseases, therefore thromboprophylaxis to prevent VTE in this setting is needed. However, thrombocytopenia and hemorrhagic complications pone many difficulties in the management of an anticoagulant or antiaggregant treatment in these patients. Recommend...

Lenalidomide in lower‚?źrisk myelodysplastic syndromes with karyotypes other than deletion 5q and refractory to erythropoiesis‚?źstimulating agents

We report on 31 consecutive lower‚?źrisk non‚?źdel(5q) MDS patients with anaemia refractory to ESA and treated with LEN in a compassionate programme, 20 of whom also received an ESA. An erythroid response was obtained in 15 patients (48%), including 10 of the 27 (37%) previously transfusion‚?źdependent (RBC‚?źTD) patients, who became transfusion‚?źindependent (RBC‚?źTI). Nine of the responders relapsed, whereas 6 (40%) were still responding and transfusion‚?źfree after 11+‚??31+‚??months. Median response duration was 24‚??months. The erythroid response rate was lower in refractory cytopenia with multilineage dysplasia (27% vs. 60%) and tended to be higher in patients treated with LEN‚??+‚??ESA (55% vs. 36%). Response duration was significantly longer in responders who obtained RBC‚?źTI and...

Reversal of T-cell tolerance in myelodysplastic syndrome through lenalidomide immune modulation

Authors: J M McDaniel, J X Zou, W Fulp, D-T Chen, A F List & P K Epling-Burnette (Source: Leukemia)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Bleeding and Thrombosis in Multiple Myeloma and Related Plasma Cell Disorders

Semin Thromb Hemost 2011; 37: 929-945DOI: 10.1055/s-0031-1297372ABSTRACTA variety of disease- and treatment-related factors affect the coagulation system and the risk of bleeding and thrombotic complications in patients with multiple myeloma (MM) and related plasma cell disorders (PCD). As commonly observed in other cancer settings, the malignant clone induces a cytokine environment responsible for a hypercoagulable state. The increase of blood viscosity and impairment of platelet and coagulation function due to circulating monoclonal proteins are considered key mechanisms in the hemostatic abnormalities frequently detected in patients with PCD. However, clinically significant bleeding is relatively rare and poorly correlated with these abnormalities. Management is often challenging becaus...

Establishing Rps6 hemizygous mice as a model for studying how ribosomal protein haploinsufficiency impairs erythropoiesis

Diamond-Blackfan anemia is a congenital hypoproliferative macrocytic anemia and 5q- syndrome myelodysplastic syndrome is an acquired hypoproliferative macrocytic anemia. Their common erythroid phenotype reflects a shared pathophysiology‚??haploinsufficiency of one of many ribosomal proteins and somatic deletion of one allele of the ribosomal protein S14 gene, respectively. Although these abnormalities lead to defective ribosome biogenesis, why ribosomal protein hemizygosity results in anemia is not certain. Here, we characterize the hematopoietic phenotype of mice lacking one allele of the ribosomal protein S6 gene. The mice have an erythroid phenotype similar to both Diamond-Blackfan anemia and the 5q- syndrome and lenalidomide therapy improves their anemia. (Source: Experimental Hematolo...

Radiotherapy and "new" drugs - new side effects?

Conclusions: The addition of molecular targeted drugs to conventional radiotherapy outside of approved regimens or clinical trials warrants a careful consideration especially when used in conjunction in hypo-fractionated regimens. Clinical trials are urgently needed in order to address the open question in regard to efficacy, early and late toxicity. (Source: Radiation Oncology)

New Hope for Mobilization Failures . . . Again

Patients undergoing peripheral blood stem cell mobilization for autologous transplantation may fail to achieve the generally accepted minimum threshold for transplantation (‚?•2 √? 106 CD34/kg) despite using optimal doses of granulocyte-colony stimiulating factor (G-CSF) or chemotherapy plus G-CSF. Failure rates vary from center to center but are felt to be highest in certain diseases such as non-Hodgkin‚??s lymphoma (NHL), Hodgkin‚??s disease (HD), and in heavily pretreated patients with multiple myeloma (MM). Although there is both vigorous debate and varying understanding of the optimal methods for mobilization (G-CSF alone versus chemotherapy plus G-CSF) there is general agreement that these diseases and various risk factors are associated with high rates of stem cell collection failur...

Horizon scanning: Follow up data for phase III study of lenalidomide in patients with high-risk smoldering multiple myeloma

Source: BioSpace Area: News Additional data from a phase III open-label study, presented at conference, demonstrated that early treatment with lenalidomide (RevlimidT) and dexamethasone followed by continuous lenalidomide delayed time to symptomatic disease and demonstrated a survival advantage compared with observation (current standard of care).. &#160; Of 119 evaluable patients, 57 were treated with lenalidomide (25 mg daily on days 1-21 of a 28-day cycle) and dexamethasone (20 mg on days 1-4 and 12-15 of a 28-day cycle) for nine four-week cycles and then continued treatment with a lower dose of lenalidomide (10 mg daily on days 1-21 of a 28-day cycle) until disease progression, while there were 62 patients in the therapeutic abstention arm. &#160; After a median follow-up of ...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Multiple myeloma: 2012 update on diagnosis, risk‚?źstratification, and management

AbstractDisease overview: Multiple myeloma accounts for ‚?ľ10% of all hematologic malignancies.Diagnosis: The diagnosis requires 10% or more clonal plasma cells on bone marrow examination or a biopsy proven plasmacytoma plus evidence of end‚?źorgan damage felt to be related to the underlying plasma‚?źcell disorder.Risk stratification: Patients with 17p deletion, t(14;16), t(14;20), or high‚?źrisk gene expression profiling signature have high‚?źrisk myeloma. Patients with t(4;14) translocation, karyotypic deletion 13, or hypodiploidy are considered to have intermediate‚?źrisk disease. All others are considered to have standard‚?źrisk myeloma.Risk‚?źadapted therapy: Standard‚?źrisk patients are treated with nonalkylator‚?źbased therapy such as lenalidomide plus low‚?źdose dexamethasone (Rd) ...

Long-term transfusion independence in del(5q) MDS patients after short term therapy with lenalidomide: 2 new cases

The introduction of the immunomodulatory drug lenalidomide has revolutionized the treatment of patients with myelodysplastic syndromes and interstitial deletion of the long arm of chromosome 5 [del5(q) MDS]. Treatment with lenalidomide results in transfusion independence in the vast majority of patients . Despite these impressive results some questions remain unresolved, among them the duration of treatment. Adding to this discussion has been the observation of a number of unexpected long term remissions in patients who stopped lenalidomide for various reasons. Here we report two additional such cases that add some new information to this interesting phenomenon. (Source: Leukemia Research)

Downregulation of BCL2 by AT‚?ź101 enhances the antileukaemic effect of lenalidomide both by an immune dependant and independent manner

SummaryOver‚?źexpression of anti‚?źapoptotic BCL2 has been reported in chronic lymphocytic leukaemia (CLL), but targeting BCL2 alone did not yield appreciable clinical results. However, it was demonstrated that BCL2 inhibitors enhanced the clinical efficacy of chemo and immunotherapeutics. Lenalidomide, an immunomodulator, is clinically effective in CLL and can enhance the anti‚?źCLL effects of CD20 targeting monoclonal antibody, rituximab. Here, we investigated the mechanism of immune‚?źdirected killing of lenalidomide in CLL and evaluated if concurrent targeting of CD20 and BCL2 can enhance this effect. In vitro treatment with lenalidomide enhanced the antibody‚?źmediated cellular cytotoxicity (ADCC) directed by rituximab in autologous leukaemic cells. Furthermore, peripheral blood monon...

Morphologic analysis in myelodysplastic syndromes with del(5q) treated with lenalidomide. A Japanese multiinstitutional study

Abstract: Lenalidomide is known to be effective in myelodysplastic syndromes (MDS) with del(5q) in improving anemia and suppressing del(5q) cells. MDS with del(5q) shows increase of nonlobulated megakaryocytes. However, histopathology of MDS with del(5q) treated with lenalidomide has not been fully studied. We investigated the morphologic changes in lenalidomide treated low- or intermediate-1-risk MDS with del(5q). All of evaluable patients showed high proportion of nonlobulated megakaryocytes. The nonlobulated megakaryocytes were markedly decreased in 6 patients during therapy in parallel with suppression of del(5q) cells. Our analysis suggests that single allele deletion of common deleted region inhibits nuclear lobulation of megakaryocytes. (Source: Leukemia Research)

Rituximab Plus Lenalidomide Active, Well Tolerated in Both Younger and Older Patients With Previously Untreated Chronic Lymphocytic Leukemia

Capsule Summary - In this nonrandomized phase II trial, ORR and CR rates were higher in patients younger than 65 years of age compared with patients 65 years of age or older. (Source: Clinical Care Options Oncology - Leukemia)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

ASH: Continuous Tx Yields Better Results in Multiple Myeloma (CME/CE)

SAN DIEGO (MedPage Today) -- Maintenance therapy with lenalidomide (Revlimid) should be the standard of care for older patients with newly diagnosed multiple myeloma who are not eligible for stem cell transplant, a researcher said here. (Source: MedPage Today Hematology/Oncology)

CC-5013-CLL-009: Lenalidomide Active, Well Tolerated at Different Starting Doses in Relapsed or Refractory Chronic Lymphocytic Leukemia

Capsule Summary - In this interim analysis at a median of 3 lenalidomide cycles, only 2 cases of serious tumor lysis syndrome have been reported, and more than one half of enrolled patients remain on treatment. (Source: Clinical Care Options Oncology - Leukemia)

Lenalidomide and Rituximab Combination Therapy Active With Durable Responses in Relapsed/Refractory Chronic Lymphocytic Leukemia

Capsule Summary - In this single-arm phase II trial, patients with fludarabine-refractory disease experienced lower response rates to lenalidomide plus rituximab compared with patients whose disease was not refractory to fludarabine; however, this subgroup analysis was limited by low patient numbers. (Source: Clinical Care Options Oncology - Leukemia)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Premiere Cooperative Group in Adult Lymphoma Research (GELA) Chooses REVLIMID for Study in Second Most Common Lymphoma Subtype

&nbsp; BOUDRY, Switzerland, Dec 14, 2011 (BUSINESS WIRE) --Celgene International S&Atilde;&nbsp;rl (Nasdaq: CELG) and the Groupe d'Etude des Lymphomes de l'Adulte (GELA) today announced the organizations have initiated an international, Phase... (Source: Drugs.com - Pharma News)

Most New Myeloma Patients Respond to CarfilzomibMost New Myeloma Patients Respond to Carfilzomib

Carfilzomib produced very promising response rates when combined with Revlimid (lenalidomide) and low dose dexamethasone in newly diagnosed multiple myeloma patients. Reuters Health Information (Source: Medscape Medical News Headlines)

New Insight Into Drug Action in Multiple MyelomaNew Insight Into Drug Action in Multiple Myeloma

Researchers report the discovery of a protein that appears to be essential for thalidomide and lenalidomide action in multiple myeloma. Medscape Medical News (Source: Medscape Today Headlines)

Severe dermatologic adverse reactions after exposure to lenalidomide in multiple myeloma patients with a positive HLA-DRB1*1501 and HLA-DQB1*0602.

Authors: Penna G, Allegra A, Romeo G, Alonci A, Cannavò A, Russo S, D'Angelo A, Petrungaro A, Musolino C PMID: 22150117 [PubMed - as supplied by publisher] (Source: Acta Oncologica)

IPH2101, a novel anti-inhibitory KIR antibody, and lenalidomide combine to enhance the natural killer cell versus multiple myeloma effect

Multiple myeloma (MM) patients who receive killer cell Ig&ndash;like receptor (KIR) ligand&ndash;mismatched, T cell&ndash;depleted, allogeneic transplantation may have a reduced risk of relapse compared with patients who receive KIR ligand&ndash;matched grafts, suggesting the importance of this signaling axis in the natural killer (NK) cell-versus-MM effect. Expanding on this concept, IPH2101 (1-7F9), an anti-inhibitory KIR mAb, enhances NK-cell function against autologous MM cells by blocking the engagement of inhibitory KIR with cognate ligands, promoting immune complex formation and NK-cell cytotoxicity specifically against MM cell targets but not normal cells. IPH2101 prevents negative regulatory signals by inhibitory KIR, whereas lenalidomide augments NK-cell function and also appears...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Effect of combined dexamethasone/lenalidomide therapy on NK cell-receptor levels in myeloma patients

(Source: Blood)

Emergence of central nervous system myeloma in the era of novel agents

AbstractAlthough multiple myeloma (MM) remains an incurable disease, considerable improvements in survival have been made with the introduction of autologous stem cell transplantation and new drugs. Central nervous system (CNS) MM is a rare complication associated with poor survival. Historically, CNS disease developed early in the course of MM; however recently, patients often present with CNS disease following multiple lines of therapy. It is hypothesized that exposure to novel agents (thalidomide, lenalidomide and bortezomib) changes the natural history of MM, increasing the lifetime risk of CNS disease. We analysed the baseline characteristics, treatment and outcome data of patients who presented with CNS MM at Peter MacCallum Cancer Centre between 2001 and 2010. Seven patients were id...

MDS: Refining existing therapy through improved biologic insights

Abstract: Advances in therapy can essentially be measured using two parameters; introduction of a new agent which benefits an increased number of patients over prevailing treatments or more selective use of an existing drug by matching it to the biologic characteristics associated with response. In reviewing the therapeutic landscape of myelodysplastic syndromes (MDS), both should be applied to gauge the advances in therapy. While several new drugs are currently in clinical trials for the treatment of MDS, three drugs were approved for use in the last decade and sufficient time has elapsed to take stock of the benefit they have produced in the outcome of patients both in terms of survival and quality of life. For the two hypomethylating agents, response remains limited to 50% patients at b...

Lenalidomide: Pneumonitis: 8 case reports

(Source: Reactions)

Targeting the Microenvironment in Hematological Malignancies: How to Condition both Stromal and Effector Cells to Overcome Cancer Spreading.

In this study, the effects of cholesterol synthesis inhibitors, such as statins, on the interaction between BMSC and T lymphocytes or on natural killer cell-mediated functions is analyzed and compared with other drugs known to act on BMSC, including thalidomide or lenalidomide. Besides lowering the plasma lipid levels, statins indeed show strong anti-inflammatory and immunomodulatory effects. On the other hand, these drugs can affect growth and survival of solid tumour and leukaemic cells, thus they have been proposed in the treatment of multiple myeloma, in association with drugs, as thalidomide, known to act on the cancer microenvironment.Kabelitz and co-workers move to the control of the balance between effector T (Teff) and regulatory T cells (Tregs). In particular they present data su...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Horizon scanning: FDA accepts new drug application for carfilzomib for relapsed/refractory multiple myeloma

Source: BioSpace Area: News According to BioSpace, the US FDA has accepted a New Drug Application (NDA) submission for carfilzomib, a next generation proteasome inhibitor, for the potential treatment of patients with relapsed and refractory multiple myeloma. &#160; The submission is based on a single-arm Phase II trial study including 266 patients with relapsed and refractory multiple myeloma who had received at least two prior therapies, including bortezomib and either thalidomide or lenalidomide. Carfilzomib is currently being studied in several clinical trials (Phase II and III) either as a single-agent or in combination with other therapies, for the treatment of multiple myeloma.&#160; The Phase III FOCUS study is to support registration in Europe; this is evaluating single-agent...

Cytokine profiles in relapsed multiple myeloma patients undergoing febrile reactions to lenalidomide.

Authors: Morita Y, Shimada T, Yamaguchi T, Rai S, Hirase C, Emoto M, Serizawa K, Taniguchi Y, Ojima M, Tatsumi Y, Ashida T, Matsumura I PMID: 22127558 [PubMed - as supplied by publisher] (Source: International Journal of Hematology)

Lenalidomide induced intrahepatic cholestasis in newly diagnosed patients of multiple myeloma

We report here one rare adverse effect, i.e., intrahepatic cholestasis related to lenalidomide, in two patients out of a total of 65 newly diagnosed cases of multiple myeloma receiving MPL regimen in our series. As the use of lenalidomide will increase in the future for multiple myeloma and other diseases, clinicians should be aware of this entity. Content Type Journal ArticleCategory Short CommunicationPages 1-4DOI 10.1007/s00228-011-1152-yAuthors Rabindra Kumar Jena, Department of Clinical Hematology, S.C.B. Medical College and Hospital, Cuttack, 753007 Odisha, IndiaTrupti Rekha Swain, Pharmacology Department, Clinical Pharmacology Unit, S.C.B. Medical College and Hospital, Cuttack, 753007 Odisha, IndiaSandeep Sadashivrao Kansurkar, Medicine Department, S.C.B. Medical College a...

Revlimid (lenalidomide) Fails to Help Prostate CancerRevlimid (lenalidomide) Fails to Help Prostate Cancer

A phase III trial of Revlimid (lenalidomide) for prostate cancer is stopped after it was determined that it would not extend survival. Reuters Health Information (Source: Medscape Medical News Headlines)

Plasma and cerebrospinal fluid pharmacokinetics of thalidomide and lenalidomide in nonhuman primates

Conclusion&nbsp;&nbsp;Thalidomide and lenalidomide penetrate into the CSF after oral administration of clinically relevant doses. Plasma exposure to lenalidomide was similar in our model to that observed in studies involving children who have brain tumors. These results support further development of lenalidomide for the treatment of central nervous system malignancies. Content Type Journal ArticleCategory Original ArticlePages 1-5DOI 10.1007/s00280-011-1781-yAuthors Jodi A. Muscal, Texas Children‚??s Cancer Center, Baylor College of Medicine, 1102 Bates Street, Suite 1220, Houston, TX 77030, USAYongkai Sun, Celgene Corporation, Summit, NJ, USAJed G. Nuchtern, Department of Surgery, Texas Children‚??s Hospital, Baylor College of Medicine, Houston, TX, USARobert C. Dauser, Depa...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Celgene Ends Revlimid Prostate Cancer Trial

NEW YORK (AP)&nbsp;- Celgene Corp. said Tuesday it is ending a late-stage clinical study of its drug Revlimid as a treatment for prostate cancer. Celgene said an early analysis of data showed that patients who were treated with Revlimid were not... (Source: Drugs.com - Pharma News)

Study of lenalidomide for prostate cancer stopped due to lack of efficacy

Source: Reuters Health News Area: News According to Reuters, a Phase III study evaluating lenalidomide (Revlimid¬ģ) in the treatment of castrate-resistant prostate cancer is being stopped, after the independent monitoring committee concluded that its addition to standard treatments (docetaxel and prednisone) would not significantly increase overall survival.&#160; (Source: NeLM - News)

A comparison of lenalidomide/dexamethasone versus cyclophosphamide/lenalidomide/dexamethasone versus cyclophosphamide/bortezomib/dexamethasone in newly diagnosed multiple myeloma

In conclusion, CyBorD demonstrated superior responses and less frequent serious toxicity but more neuropathy when compared to RD and CRD. Importantly, 80% of patients treated with modern therapeutic approaches are alive at 4‚??years. (Source: British Journal of Haematology)

Drug interaction between lenalidomide and itraconazole

(Source: American Journal of Hematology)

The immunomodulatory drug lenalidomide restores a vitamin D sensitive phenotype to the vitamin D resistant breast cancer cell line MDA-MB-231 through inhibition of BCL-2: potential for breast cancer therapeutics

Abstract&nbsp;&nbsp;1őĪ,25-Dihydroxyvitamin D3, (1,25-D3) the biologically active form of vitamin-D, is well established as a cancer cell growth inhibitor in addition to maintaining bone mineralization. In breast cancer cells, inhibitory effects on angiogenesis, and metastasis have been observed together with enhancement of apoptosis and induction of cell cycle arrest. There is a correlation between vitamin-D receptor expression on breast cancer cells and patient survival. However vitamin-D resistance and hypercalcaemia are key limiting factors in clinical use. The IMiD¬ģ immunomodulatory drug lenalidomide, (Revlimid¬ģ, CC-5013) used in myeloma, can also modulate apoptotic and growth signalling. We studied whether lenalidomide treated breast cancer cells would acquire sensitivity to 1...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Lenalidomide proved effective in multisystem Langerhans cell histiocytosis.

Authors: Szturz P, Adam Z, Reh√°k Z, Koukalov√° R, Slaisov√° R, Stehl√≠kov√° O, Chovancov√° J, Klabusay M, Krejńć√≠ M, Pour L, H√°jek R, Mayer J PMID: 22103591 [PubMed - as supplied by publisher] (Source: Acta Oncologica)

Light chain (AL) amyloidosis: update on diagnosis and management

Light chain (AL) amyloidosis is a plasma cell dyscrasia characterized by the pathologic production of fibrillar proteins comprised of monoclonal light chains which deposit in tissues and cause organ dysfunction. The diagnosis can be challenging, requiring a biopsy and often specialized testing to confirm the subtype of systemic disease. The goal of treatment is eradication of the monoclonal plasma cell population and suppression of the pathologic light chains which can result in organ improvement and extend patient survival. Standard treatment approaches include high dose melphalan (HDM) followed by autologous hematopoietic stem cell transplantation (SCT) or oral melphalan with dexamethasone (MDex). The use of novel agents (thalidomide, lenalidomide and bortezomib) alone and in combinat...

MHRA Drug Safety Update: Risk of second primary malignancy with use of lenalidomide (Revlimid) for newly diagnosed multiple myeloma

Source: MHRA Area: Evidence &#62; Medication Safety The November 2011 issue of Drug Safety Update from the MHRA features an update about the risk of a second primary malignancy associated with the use of lenalidomide. The Drug Safety Update notes that in clinical trials of newly diagnosed multiple myeloma (unauthorised indication), a four-fold increased incidence of second primary malignancy has been observed in patients receiving lenalidomide (7.0 %) compared with controls (1.8%). The median follow-up for participants with newly diagnosed myeloma in clinical trials ranged from 27.2 months to 36.5 months. However, there seems to be a smaller increased risk of second primary malignancy in patients treated with lenalidomide for relapsed or refractory myeloma-the authorised indication. &#1...

Lenalidomide in Multiple Myeloma: Current Experimental and Clinical Data

AbstractLenalidomide (LEN) is a structural analogue of Thalidomide and is currently considered a promising compound among immunomodulatory drugs (IMiDs). Following the demonstration of its potent anti‚?źangiogenic, anti‚?źinflammatory and anti‚?źneoplastic effects in preclinical models, LEN has emerged as an interesting option for the management of selective hematologic malignancies and may also have a possible role in certain solid tumors as well. It is currently approved in the second‚?źline therapy of multiple myeloma (MM) as well as in myelodysplastic syndrome characterized by 5q minus abnormalities. LEN has been found to be effective in the treatment of both of these conditions and to possess a manageable toxicity profile. In MM, a number of ongoing clinical trials are defining its ro...

Lenalidomide: First report of blaschkitis: case report

(Source: Reactions)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Risk assessment models for cancer‚?źassociated venous thromboembolism

AbstractVenous thromboembolism (VTE) is common in cancer patients, and is associated with significant morbidity and mortality. Several factors, including procoagulant agents secreted by tumor cells, immobilization, surgery, indwelling catheters, and systemic treatment (including chemotherapy), contribute to an increased risk of VTE in cancer patients. There is growing interest in instituting primary prophylaxis in high‚?źrisk patients to prevent incident (first‚?źtime) VTE events. The identification of patients at sufficiently high risk of VTE to warrant primary thromboprophylaxis is essential, as anticoagulation may be associated with a higher risk of bleeding. Current guidelines recommend the use of pharmacological thromboprophylaxis in postoperative and hospitalized cancer patients, as ...

Phase 2 trial of irinotecan and thalidomide in adults with recurrent anaplastic glioma

CONCLUSIONS:The combination of thalidomide and irinotecan did not achieve sufficient efficacy to warrant further investigation against AG, although a subset of patients experienced prolonged PFS/OS. A trial of the more potent thalidomide analogue, lenalidomide, in combination with irinotecan against AG is currently ongoing. Cancer 2011;. © 2011 American Cancer Society. (Source: Cancer)

Risk assessment models for cancer‚?źassociated venous thromboembolism

AbstractVenous thromboembolism (VTE) is common in cancer patients, and is associated with significant morbidity and mortality. Several factors, including procoagulant agents secreted by tumor cells, immobilization, surgery, indwelling catheters, and systemic treatment (including chemotherapy), contribute to an increased risk of VTE in cancer patients. There is growing interest in instituting primary prophylaxis in high‚?źrisk patients to prevent incident (first‚?źtime) VTE events. The identification of patients at sufficiently high risk of VTE to warrant primary thromboprophylaxis is essential, as anticoagulation may be associated with a higher risk of bleeding. Current guidelines recommend the use of pharmacological thromboprophylaxis in postoperative and hospitalized cancer patients, as ...

Phase 2 trial of irinotecan and thalidomide in adults with recurrent anaplastic glioma

CONCLUSIONS:The combination of thalidomide and irinotecan did not achieve sufficient efficacy to warrant further investigation against AG, although a subset of patients experienced prolonged PFS/OS. A trial of the more potent thalidomide analogue, lenalidomide, in combination with irinotecan against AG is currently ongoing. Cancer 2011;. © 2011 American Cancer Society. (Source: Cancer)

A phase 2 multicenter study of lenalidomide in relapsed or refractory classical Hodgkin lymphoma

Relapsed or refractory (rel/ref) classical Hodgkin lymphoma (cHL) remains a clinical challenge, with limited effective treatment options available after stem cell transplantation. In a multicenter phase 2 study, the efficacy of lenalidomide in rel/ref cHL patients was evaluated at a dose of 25 mg/d on days 1-21 of a 28-day cycle. Patients remained on lenalidomide until disease progression or an unacceptable adverse event (AE) occurred. Thirty-eight cHL patients were enrolled with a median of 4 (range, 2-9) prior therapies; 87% had undergone prior stem cell transplantation and 55% of patients did not respond to their last prior therapy. Of 36 evaluable patients, responses were 1 complete remission (CR), 6 partial remissions (PRs), and 5 patients with stable disease (SD) for &ge; 6 months re...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Celgene communication: Risk of second primary malignancies in patients treated with lenalidomide (Revlimid¬ģ)

Source: Celgene Europe Limited, MHRA Area: Evidence &#62; Medication Safety Celgene Europe Limited, in agreement with the European Medicines Agency and the MHRA has issued a letter to healthcare professionals about the outcome of the European CHMP review on the risk of secondary primary malignancies (SPM) in patients treated with lenalidomide (Revlimid). &#160; In clinical trials of newly diagnosed multiple myeloma (an unauthorised indication), a 4-fold increased incidence of second primary malignancies has been observed in patients receiving lenalidomide (7.0 %) compared with controls (1.8%). In the authorised indication in previously treated multiple myeloma patients, a small increase has also been observed (3.98 per 100 patient-years in lenalidomide treated group vs. 1.38 per 100 p...

POEMS syndrome with severe neurological damage clinically recovered with Lenalidomide.

Authors: Tomas JF, Giraldo P, Lecumberri R, Nistal S Abstract - PMID: 22058211 [PubMed - as supplied by publisher] (Source: Haematologica)

Salvage treatment with lenalidomide and dexamethasone in relapsed/refractory mantle cell lymphoma: clinical results and effects on microenvironment and neoangiogenic biomarkers.

Conclusions. These results confirm a favorable safety and activity profile of lenalidomide in relapsed/refractory MCL. The contribution of dexamethasone in achieving these results is unclear because of its possible detrimental effect on the immune activation generated by lenalidomide and the higher risk to develop infectious complications. (clinicaltrials.gov identifier: NCT00786851). PMID: 22058200 [PubMed - as supplied by publisher] (Source: Haematologica)

Cereblon expression is required for the antimyeloma activity of lenalidomide and pomalidomide

The precise molecular mechanism of action and targets through which thalidomide and related immunomodulatory drugs (IMiDs) exert their antitumor effects remains unclear. We investigated the role of cereblon (CRBN), a primary teratogenic target of thalidomide, in the antimyeloma activity of IMiDs. CRBN depletion is initially cytotoxic to human myeloma cells, but surviving cells with stable CRBN depletion become highly resistant to both lenalidomide and pomalidomide, but not to the unrelated drugs bortezomib, dexamethasone, and melphalan. Acquired deletion of CRBN was found to be the primary genetic event differentiating isogenic MM1.S cell lines cultured to be sensitive or resistant to lenalidomide and pomalidomide. Gene expression changes induced by lenalidomide were dramatically suppresse...

Thyroid Dysfunction from Antineoplastic Agents

Unlike cytotoxic agents that indiscriminately affect rapidly dividing cells, newer antineoplastic agents such as targeted therapies and immunotherapies are associated with thyroid dysfunction. These include tyrosine kinase inhibitors, bexarotene, radioiodine-based cancer therapies, denileukin diftitox, alemtuzumab, interferon-&alpha;, interleukin-2, ipilimumab, tremelimumab, thalidomide, and lenalidomide. Primary hypothyroidism is the most common side effect, although thyrotoxicosis and effects on thyroid-stimulating hormone secretion and thyroid hormone metabolism have also been described. Most agents cause thyroid dysfunction in 20%&ndash;50% of patients, although some have even higher rates. Despite this, physicians may overlook drug-induced thyroid dysfunction because of the complexity...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Pharmacokinetics, metabolism and excretion of [14C]-lenalidomide following oral administration in healthy male subjects

Conclusions&nbsp;&nbsp;In summary, following oral administration, lenalidomide is highly absorbed and bioavailable, metabolized minimally, and eliminated predominantly via urinary excretion in the unchanged form in humans. Content Type Journal ArticleCategory Original ArticlePages 1-9DOI 10.1007/s00280-011-1760-3Authors Nianhang Chen, Clinical Pharmacology, Celgene Corporation, 86 Morris Avenue, Summit, NJ 07920, USALian Wen, ABC Laboratories, Columbia, MO, USAHenry Lau, Clinical Pharmacology, Celgene Corporation, 86 Morris Avenue, Summit, NJ 07920, USASekhar Surapaneni, Nonclinical Development, Celgene Corporation, 86 Morris Avenue, Summit, NJ 07920, USAGondi Kumar, Nonclinical Development, Celgene Corporation, 86 Morris Avenue, Summit, NJ 07920, USA Journal Cancer Chem...

Safety, efficacy and biological predictors of response to sequential azacitidine and lenalidomide for elderly patients with acute myeloid leukemia

Authors: D A Pollyea, H E Kohrt, L Gallegos, M E Figueroa, O Abdel-Wahab, B Zhang, S Bhattacharya, J Zehnder, M Liedtke, J R Gotlib, S Coutre, C Berube, A Melnick, R Levine, B S Mitchell & B C Medeiros (Source: Leukemia)

Majority of patients receiving initial therapy with lenalidomide-based regimens can be successfully mobilized with appropriate mobilization strategies

Authors: S Sinha, M A Gertz, M Q Lacy, A Dispenzieri, S R Hayman, F K Buadi, D Dingli, I N Micallef, W J Hogan, D A Gastineau, S V Rajkumar & S K Kumar (Source: Leukemia)

Personalized therapy in multiple myeloma according to patient age and vulnerability: a report of the European Myeloma Network (EMN)

Most patients with newly diagnosed multiple myeloma (MM) are aged &gt; 65 years with 30% aged &gt; 75 years. Many elderly patients are also vulnerable because of comorbidities that complicate the management of MM. The prevalence of MM is expected to rise over time because of an aging population. Most elderly patients with MM are ineligible for autologous transplantation, and the standard treatment has, until recently, been melphalan plus prednisone. The introduction of novel agents, such as thalidomide, bortezomib, and lenalidomide, has improved outcomes; however, elderly patients with MM are more susceptible to side effects and are often unable to tolerate full drug doses. For these patients, lower-dose-intensity regimens improve the safety profile and thus optimize treatment outcome. Fur...

Dexamethasone/lenalidomide/pravastatin: Rhabdomyolysis in an elderly patient: case report

(Source: Reactions)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Lenalidomide: Pancytopenia: case report

(Source: Reactions)

Lenalidomide: Stevens-Johnson syndrome? in an elderly patient: case report

(Source: Reactions)

A Patient With a Tumor of the Ileocecal Valve

Question: A 73-year-old patient with myelodysplastic syndrome (-5q-syndrome) was treated with lenalidomide and later with a course with azacytdine. The patient now presented with abdominal pain and signs of intermittent intestinal obstruction. Colonoscopy 2 years before had been normal. Computed tomography was performed and revealed a large, obstructing tumor at the ileocecal valve. Colonoscopy revealed a round tumor 6 cm in diameter in the ascending colon involving the ileum ( A‚??B). Virtual chromoendoscopy using narrow-band imaging did not show any adenoma-like signs. An endoscopic biopsy was performed. (Source: Gastroenterology)

Serum free light chains in myeloma patients with an intact M protein by immunofixation: potential roles for response assessment and prognosis during induction therapy with novel agents

AbstractThe ascertainment of serum free light chain (sFLC) levels has been shown to be valuable in screening for the presence of plasma cell dyscrasia as well as for baseline prognosis in newly diagnosed patients. For patients with amyloidosis and those with oligo‚?źsecretory or non‚?źsecretory multiple myeloma (MM), serial measurement of sFLC has also been shown to be valuable in monitoring disease status. However, in patients with a measureable, intact monoclonal protein by immunofixation (M protein), the serial measurement of sFLC remains undefined and is currently not recommended in professional guidelines. Herein, we provide data comparing sFLC with M protein as biomarkers of response in newly diagnosed patients with MM undergoing induction therapy with the novel agents thalidomide, l...

Lenalidomide: Purpuric eruption (first report) in an elderly patient: case report

(Source: Reactions)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Biological effects and clinical significance of lenalidomide‚?źinduced tumour flare reaction in patients with chronic lymphocytic leukaemia: in vivo evidence of immune activation and antitumour response

SummaryLenalidomide has demonstrated impressive antileukaemic effects in patients with chronic lymphocytic leukaemia (CLL). The mechanism(s) by which it mediates these effects remain unclear. Clinically, CLL patients treated with lenalidomide demonstrate an acute inflammatory reaction, the tumour flare reaction that is suggestive of an immune activation phenomenon. Samples from CLL patients treated with lenalidomide were used to evaluate its effect on the tumour cell and components of its microenvironment (immune cellular and cytokine). Lenalidomide was unable to directly induce apoptosis in CLL cells in vitro, however it modulated costimulatory (CD80, CD83, CD86) surface molecules on CLL cells in vitro and in vivo. Concurrently, we demonstrated that NK cell proliferation was induced by le...

Impact of gene expression profiling-based risk stratification in patients with myeloma receiving initial therapy with lenalidomide and dexamethasone

We examined the utility of 2 GEP-based risk stratification systems among patients undergoing initial therapy with lenalidomide in the context of a phase 3 trial. Among 45 patients studied at baseline, 7 (16%) and 10 (22%), respectively, were high-risk using the GEP70 and GEP15 signatures. The median overall survival for the GEP70 high-risk group was 19 months versus not reached for the rest (hazard ratio = 14.1). Although the medians were not reached, the GEP15 also predicted a poor outcome among the high-risk patients. The C-statistic for the GEP70, GEP15, and FISH based risk stratification systems was 0.74, 0.7, and 0.7, respectively. Here we demonstrate the prognostic value for GEP risk stratification in a group of patients primarily treated with novel agents. This trial was registered ...

Clinical experience with antiangiogenic therapy in leukemia.

Authors: Wellbrock J, Fiedler W Abstract The pathological role of bone marrow angiogenesis in human leukemias has been clearly established. Bone marrow neoangiogenesis is mediated by several growth factors, such as VEGF-A, VEGF-C, angiopoietin-1 and -2, FGF, HGF, TGF-ő≤ and others secreted by leukemic cells. The prognostic relevance of microvessel density, and expression of VEGF-A and -C has been demonstrated especially in acute myeloid leukemia. In the last years, several classes of angiogenesis inhibitors have been developed blocking several angiogenic pathways. These include drugs that inhibit the VEGF (with or without blockade of FLT3) and the mTor signalling cascade. Besides, thalidomide and lenalidomide although possessing a pleiotrophic mode of action including antiangiogeni...

Antiangiogenesis in Myelodysplastic Syndrome.

Authors: Aguayo A, Armillas-Canseco FM, Mart√≠nez-Ba√Īos D Abstract One of the best examples of the bench-to-bedside paradigm in recent years could be the myelodysplastic syndromes (MDS). New insight into the pathophysiology of this heterogeneous group of diseases has led to relevant clinical changes. We have now the World Health Organization classification of MDS, the International Prognostic Score System to evaluate risk according to some clinical and laboratory parameters, and the approval by most of the regulatory agencies around the world of 5-azacitidine, decitabine and lenalidomide to treat MDS patients. In the last decade a robust body of evidence supports the importance of angiogenesis and angiogenesis related molecules as having a key role in the pathophysiology of hemato...

Interest of the association azacitidine‚??lenalidomide as frontline therapy in high-risk myelodysplasia or acute myeloid leukemia with complex karyotype

Interest of the association azacitidine&#8211;lenalidomide as frontline therapy in high-risk myelodysplasia or acute myeloid leukemia with complex karyotype Leukemia advance online publication, October 14, 2011. doi:10.1038/leu.2011.284 Authors: E Scherman, S Malak, C Perot, N C Gorin, M T Rubio & F Isnard (Source: Leukemia)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Plerixafor for Autologous Peripheral Blood Stem Cell Mobilization in Patients Previously Treated with Fludarabine or Lenalidomide

In conclusion, salvage mobilization with plerixafor plus G-CSF is successful in the majority of patients with MM previously treated with lenalidomide. In fludarabine-exposed patients, only 58% of patients will achieve successful salvage mobilization with plerixafor plus G-CSF, suggesting the need for novel mobilization regimens algorithms in this subgroup of patients. (Source: Biology of Blood and Marrow Transplantation)

Lenalidomide: from relapsed/refractory multiple myeloma to upfront therapy

Aging Health , October 2011, Vol. 7, No. 5, Pages 665-676. (Source: Future Medicine: Aging Health)

Treatment with Lenalidomide does not appear to increase the risk of leukemia progression in lower risk myelodysplastic syndrome with 5q deletion. A comparative analysis by the GFM.

Conclusions. Using a propensity score approach, we found no significant difference in acute myeloid leukemia progression and survival from diagnosis between the cohort treated with lenalidomide and the control cohort. PMID: 21993675 [PubMed - as supplied by publisher] (Source: Haematologica)

Lenalidomide in MDS: 4th time's a charm

(Source: Blood)

A randomized phase 3 study of lenalidomide versus placebo in RBC transfusion-dependent patients with Low-/Intermediate-1-risk myelodysplastic syndromes with del5q

This phase 3, randomized, double-blind study assessed the efficacy and safety of lenalidomide in 205 red blood cell (RBC) transfusion-dependent patients with International Prognostic Scoring System Low-/Intermediate-1-risk del5q31 myelodysplastic syndromes. Patients received lenalidomide 10 mg/day on days 1-21 (n = 69) or 5 mg/day on days 1-28 (n = 69) of 28-day cycles; or placebo (n = 67). Crossover to lenalidomide or higher dose was allowed after 16 weeks. More patients in the lenalidomide 10- and 5-mg groups achieved RBC-transfusion independence (TI) for &ge; 26 weeks (primary endpoint) versus placebo (56.1% and 42.6% vs 5.9%; both P &lt; .001). Median duration of RBC-TI was not reached (median follow-up, 1.55 years), with 60% to 67% of responses ongoing in patients without progression ...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Lenalidomide enhances the anti‚?źprostate cancer activity of docetaxel in vitro and in vivo

CONCLUSIONSLenalidomide may be a promising candidate for combination with docetaxel in the treatment of CRPC. Prostate © 2011 Wiley Periodicals, Inc. (Source: The Prostate)

Spotlight on Lenalidomide in Relapsed or RefractoryMultiple Myeloma

(Source: BioDrugs)

Lenalidomide enhances the anti‚?źprostate cancer activity of docetaxel in vitro and in vivo

CONCLUSIONSLenalidomide may be a promising candidate for combination with docetaxel in the treatment of CRPC. Prostate © 2011 Wiley Periodicals, Inc. (Source: The Prostate)

Prevention of venous thromboembolism in patients with cancer: Guidelines of the Italian Society for Haemostasis and Thrombosis (SISET)1

Conclusion: Results of the systematic literature review and an explicit approach to consensus techniques have led to recommendations for the most clinically important issues in the prevention of VTE in cancer patients. (Source: Thrombosis Research)

The 5q- Syndrome: Biology and Treatment

Opinion statement&nbsp;&nbsp;The 5q- syndrome is a myelodsyplastic syndrome (MDS) characterized by symptomatic anemia and an indolent natural history with low transformation potential. Our understanding of the molecular pathogenesis of this disease has advanced considerably, paralleled by the delineation of the relevant targets underlying selective lenalidomide sensitivity. The context in which one treats the 5q- syndrome, and all lower risk MDS, is critical. The focus of treatment should remain the amelioration of refractory cytopenias. In the 5q- syndrome, lenalidomide is the treatment of choice for patients with symptomatic anemia as it relieves the burden of transfusion dependence and iron overload in the majority of cases. We discuss herein the current understanding of the biolo...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Long-term transfusion independence in del(5q) MDS patients who discontinue lenalidomide

Authors: A A N Giagounidis, A Kulasekararaj, U Germing, R Radkowski, S Haase, P Petersen, G G&#246;hring, G B&#252;sche, C Aul, G J Mufti & U Platzbecker (Source: Leukemia)

Lenalidomide as initial therapy of elderly patients with chronic lymphocytic leukemia

This study was registered at www.clinicaltrials.gov as #NCT00535873. (Source: Blood)

Hematopoietic Growth Factors in Myelodysplastic Syndromes

Hematopoietic growth factors (HGFs) continue to be the most widely prescribed class of medications for patients with myelodysplastic syndromes (MDS), despite the advent of disease-modifying therapies for MDS (eg, azacitidine, decitabine, and lenalidomide) and the current absence of an MDS-specific US Food and Drug Administration (FDA)-approved indication for any of the HGFs. Erythropoiesis-stimulating agents (ESAs: epoetin alfa, darbepoetin alfa), myeloid growth factors (MGFs: filgrastim, pegfilgrastim, sargramostim), and the newest group of HGFs, thrombopoiesis-stimulating agents (TSAs: romiplostim, eltrombopag), can increase peripheral blood counts in some patients, and may ameliorate some of the signs and symptoms of MDS-associated bone marrow failure. Although HGFs are generally consid...

Role of Lenalidomide in the Treatment of Myelodysplastic Syndromes

Lenalidomide is characterized as an immunomodulatory drug (IMiD), a second-generation drug in this proprietary drug class with greater potency and a toxicity profile that is distinct from the lead compound, thalidomide. Clinical trials exploring its role in treating patients with myelodysplastic syndrome (MDS) revealed unique karyotype-specific activity in patients with interstitial deletion of the long arm of chromosome 5 (del(5q)). This observation ultimately led the US Food and Drug Administration (FDA) to approve lenalidomide for the treatment of lower risk transfusion-dependent patients with del(5q) MDS. Herein we review the results of four clinical trials conducted with lenalidomide in lower risk MDS, summarizing the clinical efficacy and safety of the drug. We discuss the use of len...

Benefit-Risk Balance Of Multiple Myeloma Treatment Revlimid Remains Positive

According to confirmation from the European Medicines Agency the benefit-risk balance for Revlimid (lenalidomide) remains positive within its approved patient population, however, doctors are advised of the risk of new cancers as a result of treatment with the medicine. Revlimid is administered in combination with dexamethasone, an anti-inflammatory medicine, to treat adult patients with multiple myeloma whose disease has been treated at least once in the past... (Source: Health News from Medical News Today)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Continuous treatment in multiple myeloma - ready for prime time?

Authors: Knop S Abstract Recently, non-genotoxic drugs have succeeded in several hematologic malignancies such as chronic myeloid leukemia (CML) or indolent non-Hodgkin's lymphomas. Unlike this, alkylating chemotherapy is still a backbone of anti-myeloma drug treatment in the vast majority of 'medically fit' subjects. With the introduction of the immunomodulatory drugs thalidomide and lenalidomide, a novel class of compounds was integrated into therapy of multiple myeloma. Either drug may be delivered for a prolonged time; however fatigue, constipation and neuropathy prevent thalidomide from serving as a 'continuous' treatment. Lenalidomide has been approved for treatment of relapsed multiple myeloma, to be delivered as a continuous therapy. Since the drug lacks thalidomide's sever...

Lenalidomide Has Positive Benefit/Risk Ratio, Says EMALenalidomide Has Positive Benefit/Risk Ratio, Says EMA

The benefit/risk balance for lenalidomide remains positive within its approved population, according to the European Medicines Agency (EMA). Medscape Medical News (Source: Medscape Today Headlines)

European Medicines Agency Concludes That Benefit-Risk Balance of Revlimid Remains Positive

The European Medicines Agency has confirmed that the benefit-risk balance for Revlimid (lenalidomide) remains positive within its approved patient population but advises doctors of the risk of new cancers as a result of treatment with the... (Source: Drugs.com - Pharma News)

European Medicines Agency concludes that benefit-risk balance of lenalidomide (Revlimid¬ģ) remains positive

Source: European Medicines Agency (EMA) Area: News The European Medicines Agency has confirmed that the benefit-risk balance for lenalidomide (Revlimid¬ģ) remains positive within its approved patient population but advises prescribers of the risk of new cancers as a result of treatment with it. Lenalidomide is used in combination with dexamethasone in adults for the treatment of multiple myeloma whose disease has been previously treated at least once. The review of lenalidomide was initiated following the results of three new studies showing a higher rate of new cancers in patients with newly diagnosed multiple myeloma who were being treated with lenalidomide and who received other treatments concomitantly. The studies showed a four-fold increase in the number of new cancers in patients...

Revlimid (lenalidomide) wins positive opinion in Europe, despite dangers

(Source: Modern Medicine)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Pomalidomide plus low-dose dexamethasone in myeloma refractory to both bortezomib and lenalidomide: comparison of 2 dosing strategies in dual-refractory disease

Pomalidomide at doses of 2 or 4 mg/d has demonstrated excellent activity in patients with multiple myeloma (MM). We opened 2 sequential phase 2 trials using the pomalidomide with weekly dexamethasone (Pom/dex) regimen at differing doses to study the efficacy of this regimen in patients who have failed both lenalidomide and bortezomib. Pomalidomide was given orally 2 or 4 mg daily with dexamethasone 40 mg weekly. Thirty-five patients were enrolled in each cohort. Confirmed responses in the 2-mg cohort consisted of very good partial response (VGPR) in 5 (14%), partial response (PR) in 4 (11%), minor response (MR) in 8 (23%) for an overall response rate of 49%. In the 4-mg cohort, confirmed responses consisted of complete response (CR) in 1 (3%), VGPR in 3 (9%), PR in 6 (17%), MR in 5 (14%) f...

Thrombotic complications in multiple myeloma: a report of three cases and review of the literature

We report 3 cases of MM with VTE with review of the literature. This review highlights the risk factors for VTE in MM and general, disease-specific and treatment-related mechanisms for thrombosis. Content Type Journal ArticlePages 1-5DOI 10.1007/s11239-011-0636-zAuthors Yonal Ipek, Department of Internal Medicine, Division of Hematology, Istanbul University Istanbul Medical Faculty, Istanbul, TurkeyHindilerden Fehmi, Department of Internal Medicine, Division of Hematology, Istanbul University Istanbul Medical Faculty, Istanbul, TurkeyBesisik-Kalayoglu Sevgi, Department of Internal Medicine, Division of Hematology, Istanbul University Istanbul Medical Faculty, Istanbul, TurkeySargin Deniz, Department of Internal Medicine, Division of Hematology, Istanbul University Istanbul Medical...

Impact of high‚?źrisk classification by FISH: an Eastern Cooperative Oncology Group (ECOG) study E4A03

SummaryLenalidomide with dexamethasone is a standard induction treatment regimen for newly diagnosed myeloma (although a Federal Drug Administration indication is still absent). In the context of the Phase 3 clinical trial E4A03 (lenalidomide plus dexamethasone in low or high doses), we queried whether a fluorescence in situ hybridization (FISH)‚?źbased genetic classification into high risk (HR) and standard risk (SR) multiple myeloma (MM) would remain clinically significant. Of 445 E4A03 patients, 126 had FISH analysis; 21 were classified HR with t(4;14), t(14;16), or 17p13 deletions. Median survival follow‚?źup approached 3‚??years. Patients with FISH data tended to be younger and healthier compared to the rest of the study population and, consequently, had superior overall survival (OS)...

Cytogenetic and Molecular Abnormalities in Myelodysplastic Syndrome.

Authors: Nagoshi H, Horiike S, Kuroda J, Taniwaki M Abstract Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematological disorders characterized by ineffective hematopoiesis which causes peripheral cytopenias and a risk of progression to acute myeloid leukemia. Although various forms of chromosomal abnormalities have been detected in approximately 50-60% of patients with de novo MDS and in up to 80% of patients with therapy-related MDS, their molecular significance for pathogenesis and disease progression is not yet fully understood. Recent technical advances in molecular biology have disclosed more accurately details of pathological chromosomal and molecular aberrations in MDS. Such details could not be identified with conventional cytogenetical techniques, inc...

Novel therapies in MM: from the aspect of preclinical studies.

Authors: Hideshima T, Anderson KC Abstract During the last decade, thalidomide, lenalidomide, and bortezomib have been approved by the US Food and Drug Administration for the treatment of MM; however, MM remains incurable. The development and progression of multiple myeloma (MM) is a complex multi-step process involving genetic abnormalities in tumor cells at both early and late stages. Moreover, soluble factors and cell-cell contact within the tumor bone marrow (BM) microenvironment promotes MM cell growth, survival, and drug resistance. A number of novel agents targeting both tumor cells and growth factors in the BM milieu have been developed. Currently they are under evaluation in preclinical studies, as single agents and/or in combination, to improve outcome of MM patients. ...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Serum free light chains in myeloma patients with an intact M protein by immunofixation: potential roles for response assessment and prognosis during induction therapy with novel agents

AbstractThe ascertainment of serum free light chain (sFLC) levels has been shown to be valuable in screening for the presence of plasma cell dyscrasia as well as for baseline prognosis in newly diagnosed patients. For patients with amyloidosis and those with oligo‚?źsecretory or non‚?źsecretory multiple myeloma (MM), serial measurement of sFLC has also been shown to be valuable in monitoring disease status. However, in patients with a measureable, intact monoclonal protein by immunofixation (M protein), the serial measurement of sFLC remains undefined and is currently not recommended in professional guidelines. Herein, we provide data comparing sFLC with M protein as biomarkers of response in newly diagnosed patients with MM undergoing induction therapy with the novel agents thalidomide, l...

Emergence of central nervous system myeloma in the era of novel agents

AbstractAlthough multiple myeloma (MM) remains an incurable disease, considerable improvements in survival have been made with the introduction of autologous stem cell transplantation and new drugs. Central nervous system (CNS) MM is a rare complication associated with poor survival. Historically, CNS disease developed early in the course of MM; however recently, patients often present with CNS disease following multiple lines of therapy. It is hypothesized that exposure to novel agents (thalidomide, lenalidomide and bortezomib) changes the natural history of MM, increasing the lifetime risk of CNS disease. We analysed the baseline characteristics, treatment and outcome data of patients who presented with CNS MM at Peter MacCallum Cancer Centre between 2001 and 2010. Seven patients were id...

A phase 2 randomized multicenter study of 2 extended dosing schedules of oral ezatiostat in low to intermediate‚?ź1 risk myelodysplastic syndrome

CONCLUSIONS:Ezatiostat is the first GSTP1‚?ź1 inhibitor shown to cause clinically significant and sustained reduction in RBC transfusions, transfusion independence, and multilineage responses in MDS patients. The tolerability and activity profile of ezatiostat may offer a new treatment option for patients with MDS. Cancer 2012. ¬© 2011 American Cancer Society. (Source: Cancer)

Lenalidomide maintenance after nonmyeloablative allogeneic stem cell transplantation in multiple myeloma is not feasible: results of the HOVON 76 Trial

In conclusion, lenalidomide maintenance 10 mg daily after nonmyeloablative allo-SCT with unmanipulated graft in multiple myeloma patients is not feasible, mainly because of the induction of acute GVHD. This trial was registered at www.trialregister.nl as #NTR1645. (Source: Blood)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Reply to tumor flare reaction associated with lenalidomide treatment in patients with chronic lymphocytic leukemia predicts clinical response

(Source: Cancer)

Phase I Trial of Lenalidomide and CCI-779 in Patients With Relapsed Multiple Myeloma: Evidence for Lenalidomide-CCI-779 Interaction via P-Glycoprotein [Phase I and Clinical Pharmacology]

Conclusion The MTD of this combination regimen was 25 mg lenalidomide with 15 mg CCI-779, with toxicities of fatigue, neutropenia, and electrolyte wasting. Pharmacokinetic and clinical interactions between lenalidomide and CCI-779 seemed to occur, with in vitro data indicating lenalidomide was an ABCB1 (P-gp) substrate. To our knowledge, this is the first report of a clinically significant P-gp&ndash;based drug-drug interaction with lenalidomide. (Source: Journal of Clinical Oncology)

Changes in PSA kinetics predict metastasis‚?źfree survival in men with PSA‚?źrecurrent prostate cancer treated with nonhormonal agents

CONCLUSIONS:This hypothesis‚?źgenerating analysis suggests that within‚?źsubject changes in PSADT and PSA slope after initiation of experimental therapy may correlate with MFS in men with biochemically recurrent prostate cancer. If validated in prospective trials, changes in PSA kinetics may represent a reasonable intermediate end point for screening new agents in these patients. Cancer 2011;. ¬© 2011 American Cancer Society. (Source: Cancer)

Extramedullary intracranial localization of multiple myeloma and treatment with novel agents: A retrospective survey of 50 patients

CONCLUSIONS:The overall data highlight the relevance of therapy with new drugs in intracranial myeloma, providing a framework for future clinical trials. Cancer 2011;. © 2011 American Cancer Society. (Source: Cancer)

Dexamethasone and lenalidomide have distinct functional effects on erythropoiesis

Corticosteroids and lenalidomide decrease red blood cell transfusion dependence in patients with Diamond-Blackfan anemia (DBA) and myelodysplastic syndrome (MDS), respectively. We explored the effects of dexamethasone and lenalidomide, individually and in combination, on the differentiation of primary human bone marrow progenitor cells in vitro. Both agents promote erythropoiesis, increasing the absolute number of erythroid cells produced from normal CD34+ cells and from CD34+ cells with the types of ribosome dysfunction found in DBA and del(5q) MDS. However, the drugs had distinct effects on the production of erythroid progenitor colonies; dexamethasone selectively increased the number of burst-forming units-erythroid (BFU-E), whereas lenalidomide specifically increased colony-forming uni...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Parvovirus B19-induced Type II Mixed Cryoglobulinemia

We report on a patient with type II mixed cryoglobulinemia due to acute infection with parvovirus B19 who was treated successfully with lenalidomide. (Source: The American Journal of Medicine)

Pulmonary alveolar hemorrhage possibly associated with lenalidomide use.

Authors: Oshima Y, Tojo A PMID: 21858442 [PubMed - as supplied by publisher] (Source: International Journal of Hematology)

Therapeutic effect of Lenalidomide in a novel xenograft mouse model of human Blastic NK cell lymphoma/blastic plasmacytoid dendritic cell neoplasm.

CONCLUSIONS: Our BNKL model might better define the cellular and molecular mechanisms involved in this disease, and lenalidomide might be considered for the future therapy of BNKL patients. PMID: 21856771 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Complete Remission with a Combination of Lenalidomide, Cyclophosphamide and Prednisolone in a Patient with Incomplete POEMS Syndrome.

Authors: SuyanńĪ E, Yań?cńĪ M, Sucak GT Abstract No abstract available. PMID: 21849771 [PubMed - as supplied by publisher] (Source: Acta Haematologica)

Efficacy of retreatment with immunomodulatory drugs (IMiDs) in patients receiving IMiDs for initial therapy of newly diagnosed multiple myeloma

The efficacy of retreatment with immunomodulatory drugs (IMiDs) among patients with multiple myeloma who received this class of drugs for initial therapy is unknown. We studied 140 patients who received either thalidomide-dexamethasone (81; 58%) or lenalidomide-dexamethasone (59; 42%) as first-line therapy of multiple myeloma followed by repeat IMiD (thalidomide [34; 24%] or lenalidomide [106; 76%]) as one of the salvage regimens. A median of 2 treatments (range, 1-6), including a stem cell transplant in 105 patients (75%), were administered before IMiD-based salvage therapy. The median time from diagnosis to repeat exposure to IMiD was 28 months. Among the 113 evaluable patients, 50 (44%) achieved at least a partial response, and 63 (56%) achieved less than a partial response to repeat IM...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

In Vitro and In Vivo Selective Antitumor Activity of a Novel Orally Bioavailable Proteasome Inhibitor MLN9708 against Multiple Myeloma Cells.

CONCLUSION: Our preclinical study supports clinical evaluation of MLN9708, alone or in combination, as a potential MM therapy. Clin Cancer Res; 17(16); 5311-21. ©2011 AACR. PMID: 21724551 [PubMed - in process] (Source: Clinical Lymphoma and Myeloma)

Lenalidomide-induced purpuric eruption: A new adverse cutaneous reaction

We report a purpuric drug eruption in a patient with primary systemic amyloidosis receiving lenalidomide therapy. (Source: Journal of the American Academy of Dermatology)

Surprise: Lenalidomide May Interact With P-GlycoproteinSurprise: Lenalidomide May Interact With P-Glycoprotein

Medscape Medical News (Source: Medscape Today Headlines)

Study Urges Caution With Lenalidomide Dosage

An early phase multiple myeloma trial has unexpectedly revealed that the drug lenalidomide interacts with another protein in cells that affect its dose level in the body, say researchers at the Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James) who conducted the study. Lenalidomide is an anti-inflammatory drug, and more than 390 clinical trials have been initiated to study its activity in a number of cancers and other diseases... (Source: Health News from Medical News Today)

NICE work programme referrals - July 2011

Source: Department of Health (DH) Area: News Ministers have agreed that the following single technology appraisal topics should be finally referred to the NICE work programme: &nbsp; .&nbsp;Botulinum toxin type A for the prophylaxis of headaches associated with chronic migraine &nbsp; .&nbsp;Lenalidomide for the maintenance treatment of multiple myeloma after autologous stem cell transplantation &nbsp; .&nbsp;Lenalidomide as induction therapy for newly diagnosed multiple myeloma &nbsp; .&nbsp;Lenalidomide as maintenance therapy for newly diagnosed multiple myeloma in people who have previously received induction chemotherapy &nbsp; .&nbsp;Lenalidomide for the treatment of myelodysplastic syndromes associated with a deletion 5q cytogenetic abnormality in people with red...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

IMiDs in hematology.

Authors: Wémeau M, Gauthier J, Leleu X, Yakoub-Agha I Abstract IMiDs belong to a new pharmalogical class, whose principal therapeutic agents are the thalidomide and the lenalidomide. They have immunomodulatory and antiangiogenic properties, as well as a direct effect on tumor cells. Thalidomide and lenalidomide were first approved for multiple myeloma, and in 5q-myelodysplastic syndrome for lenalidomide. Several studies have shown the efficacy of these drugs in others hematologic malignancies. A third component has been developed, the pomalidomide, which may be more effective in certain indications. Here we present an overview of IMiDs in hematology, including mechanisms of action and known significant side effects. PMID: 21827980 [PubMed - as supplied by publisher] (Source: B...

Study urges caution with lenalidomide dosage

(Ohio State University Medical Center) An early phase myeloma trial has unexpectedly revealed that the drug lenalidomide interacts with another protein in cells that affect its dose level in the body. The drug is under study in more than 390 clinical trials for cancer and other diseases, and sometimes causes severe and life-threatening side effects. The findings could lead to safer dosing of lenalidomide in a variety of diseases. (Source: EurekAlert! - Cancer)

Lenalidomide therapy in treatment-refractory cutaneous lupus erythematosus: Histologic and circulating leukocyte profile and potential risk of a systemic lupus flare

Conclusions: Lenalidomide may have usefulness as therapy for severe, treatment-refractory CLE. However, our preliminary data suggest that lenalidomide may activate T cells and trigger systemic disease in some patients with CLE. We also saw a different histologic and circulating leukocyte phenotype in the nonresponding subject. Further characterization of the skin and circulating leukocyte profile of treatment-refractory patients will improve our understanding of CLE. (Source: Journal of the American Academy of Dermatology)

Significant interactions between lenalidomide and CCI-779

NEW YORK (Reuters Health) - The immunomodulator lenalidomide and the mammalian target of rapamycin (mTOR) inhibitor CCI-779 interact to increase each other's blood levels, according to new findings. (Source: Modern Medicine)

Lenalidomide in combination with dexamethasone induced rhabdomyolysis in a multiple myeloma patient treated with pravastatin.

Authors: Urata C, Yoshimura M, Itamura H, Hisatomi T, Kubota Y, Fukushima N, Sueoka E, Kimura S PMID: 21811773 [PubMed - as supplied by publisher] (Source: International Journal of Hematology)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Novel agents‚?źbased regimens as induction treatment prior to autologous stem‚?źcell transplantation in newly diagnosed multiple myeloma: a meta‚?źanalysis of randomized controlled trials

In conclusion, our analysis showed novel agents as induction treatment prior to ASCT improved CR and PFS but not OS. Copyright © 2011 John Wiley & Sons, Ltd. (Source: Hematological Oncology)

Acute lung toxicity related to pomalidomide.

In this report, we review the course of two patients receiving pomalidomide therapy who subsequently developed dyspnea, fever, hypoxia, and ground-glass opacities on CT scan. An extensive workup for infectious causes was negative. Both patients improved with discontinuation of the medication and/or treatment with corticosteroids. Both patients were restarted on pomalidomide therapy at a lower dose, with one patient experiencing an immediate recurrence of pulmonary symptoms. The combination of symptoms, radiographic findings, clinical course, and response to treatment strongly supports the diagnosis of acute pulmonary toxicity secondary to pomalidomide. We then review previously published pulmonary toxicity data on thalidomide and lenalidomide and compare the described clinical courses, rad...

Anti-myelin associated glycoprotein neuropathy responding to lenalidomide

Monoclonal gammopathies are a heterogeneous group of disorders which include monoclonal gammopathy of unknown significance (MGUS), multiple myeloma (MM), solitary plasmacytoma, Waldenström's macroglobulinemia (WM), and primary amyloidosis. There is a known association between monoclonal gammopathy and neuropathy, however, the pathogenesis of this association has only recently been clarified. Several different neural antigenic sites have been identified, the most important of which is myelin-associated glycoprotein (MAG). Anti-MAG IgM is present in half of all patients with IgM monoclonal gammopathy-related neuropathy and it has therefore been suggested that reducing anti-MAG IgM may present a strategy to improve gammopathy-related neuropathy . (Source: Leukemia Research)

Telomere shortening, clonal evolution and disease progression in myelodysplastic syndrome patients with 5q deletion treated with lenalidomide

Authors: G G&#246;hring, K Lange, W Hofmann, K V Nielsen, E Hellstr&#246;m-Lindberg, L Roy, M Morgan, H Kreipe, G B&#252;sche, A Giagounidis & B Schlegelberger (Source: Leukemia)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Comparison of thalidomide and lenalidomide as therapy for myelofibrosis

In conclusion, the combination of lenalidomide plus prednisone appears to be more ef-fective and safer than single-agent thalidomide or lenalidomide. (Source: Blood)

Lenalidomide associated with durable remissions in elderly patients with symptomatic CLL

Badoux XC. Blood. 2011;doi:10.1182/blood-2011-03-339077. (Source: HemOncToday.com)

Monoclonal antibodies in the treatment of multiple myeloma

SummaryDespite recent advances in treatment that have significantly improved overall survival, multiple myeloma (MM) remains incurable. Although rituximab, the first monoclonal antibody (MAb) evaluated in MM treatment, provided only very limited benefit, research is ongoing into a number of other MAbs directed against a variety of MM‚?źrelated target antigens. Given the inherent immune dysfunction associated with MM, newer strategies that may enhance immune function in conjunction with antibodies may also provide a more fruitful clinical approach. Potential MAb targets in MM include growth factors and their receptors, other signalling molecules, and antigens expressed exclusively or predominantly on MM cells. MAb therapy involves a range of mechanisms, including antibody‚?źdependent cellul...

Lenalidomide in AML: Del(5q) or who?

(Source: Blood)

A phase 2 study of lenalidomide monotherapy in patients with deletion 5q acute myeloid leukemia: Southwest Oncology Group Study S0605

In conclusion, lenalidomide as a single agent has modest activity in older del(5q) AML patients. Southwest Oncology Group Study S0605 is registered at www.clinicaltrials.gov as NCT00352365. (Source: Blood)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Lenalidomide, bortezomib, pegylated liposomal doxorubicin, and dexamethasone in newly diagnosed multiple myeloma: a phase 1/2 Multiple Myeloma Research Consortium trial

This phase 1/2 trial evaluated combination lenalidomide, bortezomib, pegylated liposomal doxorubicin, and dexamethasone (RVDD) in newly diagnosed multiple myeloma (MM) patients. Patients received RVDD at 4 dose levels, including the maximum tolerated dose (MTD). Patients with a very good partial response or better (&ge; VGPR) after cycle 4 proceeded to autologous stem cell transplantation or continued treatment. The primary objectives were MTD evaluation and response to RVDD after 4 and 8 cycles. Seventy-two patients received a median of 4.5 cycles. The MTDs were lenalidomide 25 mg, bortezomib 1.3 mg/m2, pegylated liposomal doxorubicin 30 mg/m2, and dexamethasone 20/10 mg, as established with 3-week cycles. The most common adverse events were fatigue, constipation, sensory neuropathy, and ...

Lenalidomide for aggressive B‚?źcell lymphoma involving the central nervous system?

AbstractLymphomas arising or relapsing in the central nervous system (CNS) have a dismal prognosis[1]. Very few active drugs passing through the blood brain barrier are available. Lenalidomide is a novel and extremely active compound in relapsed diffuse‚?źlarge‚?źB‚?źcell‚?źlymphoma (DLBCL) and mantle cell lymphoma (MCL) [2‚?ź3]. The pleiotropic action of Lenalidomide needs to be further exploited in different clinical settings and in combination with other drugs [4‚?ź5]. Thus far, patients with aggressive lymphomas and CNS involvement have been excluded from clinical trials and there are no data about Lenalidomide penetration in the CNS. Very recently it was reported that Lenalidomide induced remission in a case of DLBCL relapsed within the CNS [6]. Here we refer on a case of blastoid MCL...

Lenalidomide: Exacerbation of hypothyroidism in an elderly patient: case report

(Source: Reactions)

Lenalidomide: Fatal ischaemic stroke in a patient with multiple myeloma: case report

(Source: Reactions)

Lenalidomide in del 5q MDS: Responses and side effects revisited

Lenalidomide is a milestone in the therapeutic management of myelodysplastic syndromes (MDS), especially in those with del 5q abnormalities. It is currently approved by the Food and Drug Administration for the treatment of low and intermediate-1 risk MDS patients with transfusion-dependent anemia associated with deletion 5q with or without additional chromosomal abnormalities. Lenalidomide belongs to a class of second generation immunomodulatory drugs (IMiDs) that traces its lineage to thalidomide. However, despite its success as a drug in MDS, the exact mechanism of action remains elusive. Several experimental studies have provided some hints. Wei et al. attributed the increased lenalidomide sensitivity of MDS patients with del 5q to the haploinsufficiency of two dual specificity phosphat...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Efficacy of lenalidomide in a patient with myelodysplastic syndrome with isolated del(5q) and JAK2V617F mutation

The efficacy of lenalidomide in the acquisition of transfusion independence and even cytogenetic remission in a high proportion of transfusion-dependent lower-risk patients with MDS and del(5q) has been demonstrated . However, it is not known whether the presence of a concomitant JAK2V617F mutation might influence such favorable results. (Source: Leukemia Research)

Lenalidomide-Associated ITP

Lenalidomide is a potent immunomodulatory agent being used increasingly for treatment of hematologic malignancies including multiple myeloma and myelodysplasia. The common toxicities of lenalidomide, including dose-limiting myelosuppression, are well described. However, the immunomodulatory properties of lenalidomide may give rise to unexpected autoimmune complications. Herein, we describe a case of immune thrombocytopenic purpura (ITP) associated with use of lenalidomide. (Source: Journal of Biomedicine and Biotechnology)

Tumor flare reaction associated with lenalidomide treatment in patients with chronic lymphocytic leukemia predicts clinical response

(Source: Cancer)

Lenalidomide‚?źassociated Pneumonitis in patients with plasma cell dyscrasias

AbstractLenalidomide is an immunomodulatory drug (IMiD) that has been approved for the treatment of relapsed or refractory MM (1, 2). Common side effects of lenalidomide treatment include myelosupression, diarrhea, fever, muscle cramps, neuropathy, constipation, rash, fatigue, and deep vein thrombosis (1‚??4). Pulmonary complications are believed to be uncommon. So far three cases of lenalidomide‚?źinduced pulmonary toxicity have been reported commonly presented with dyspnea, fever and hypoxia (5‚??7). In order to assess the incidence, characteristics and outcome of pneumonitis associated with lenalidomide we assessed the incidence and outcome of lenalidomide‚?źinduced pneumonitis in 237 consecutive unselected patients with multiple myeloma or AL amyloidosis. We identified 8 (3.37%) patien...

Lenalidomide: Hepatitis: case report

(Source: Reactions)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

In vitro effects of perifosine, bortezomib and lenalidomide against hematopoietic progenitor cells from healthy donors

Summary&nbsp;&nbsp;The novel AKT inhibitor perifosine possesses myelopoiesis-stimulating effects in rodents. We studied the in vitro effects of the novel agents perifosine, bortezomib and lenalidomide in addition to adriamycin against normal human hematopoietic progenitor cells (HPC) using different clonogenic and non-clonogenic assays. All agents inhibited colony-forming unit (CFU) formation, perifosine inhibiting mainly CFU-granulocyte/macrophage formation and the other agents burst-forming unit-erythroid formation. Perifosine combined with lenalidomide or adriamycin tended to act antagonistically in suppressing CFU formation. Despite their inhibition of CFU formation, perifosine, bortezomib and lenalidomide induced only slight or moderate cytotoxicity in CD34+ selected HPC, as asse...

Impact of lenalidomide dose on progression-free survival in patients with relapsed or refractory multiple myeloma

Authors: M A Dimopoulos, M Hussein, A S Swern & D Weber (Source: Leukemia)

Lenalidomide modulates IL‚?ź8 and anti‚?źprostate antibody levels in men with biochemically recurrent prostate cancer

CONCLUSIONSLenalidomide demonstrates immunomodulatory properties in patients with biochemically recurrent prostate cancer. The induction of novel anti‚?źprostate antibodies is a potential mechanism for lenalidomide response. Changes in serum IL‚?ź8 levels may serve as a potential biomarker in treated patients. These hypotheses require formal testing in future prospective trials. Prostate ¬© 2011 Wiley‚?źLiss, Inc. (Source: The Prostate)

MHRA Drug Safety Update: risk of arterial and venous thromboembolism with thalidomide

Source: MHRA Area: Evidence > Medication Safety The July 2011 issue of Drug Safety Update includes a reminder of the increased risk of arterial thromboembolism, including myocardial infarction and cerebrovascular events, associated with use of thalidomide.&nbsp; This is in addition to the established risk of venous thromboembolism associated with the drug. &nbsp; The article discusses post-marketing case reports of thrombosis and thromboembolic reactions reported in association with thalidomide; evidence suggests that the risk is highest during the first five months of treatment.&nbsp; The pathophysiology of arterial thrombosis in patients treated with thalidomide is not fully understood; it appears to be an effect associated with the drug class (the MHRA has recently reported a simil...

Regression of Refractory Intraocular Large B-Cell Lymphoma With Lenalidomide Monotherapy [DIAGNOSIS IN ONCOLOGY]

(Source: Journal of Clinical Oncology)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Lenalidomide can be safely combined with R-CHOP (R2CHOP) in the initial chemotherapy for aggressive B-cell lymphomas: phase I study

Authors: G S Nowakowski, B LaPlant, T M Habermann, C E Rivera, W R Macon, D J Inwards, I N Micallef, P B Johnston, L F Porrata, S M Ansell, R R Klebig, C B Reeder & T E Witzig (Source: Leukemia)

Clinical effect of increasing doses of lenalidomide in high-risk myelodysplastic syndrome and acute myeloid leukemia with chromosome 5 abnormalities.

Conclusions Our data support a role for higher doses of lenalidomide in poor prognosis patients with myelodysplastic syndrome and acute myeloid leukemia with deletion 5q. (Clinicaltrials.gov identifier NCT00761449). PMID: 21719884 [PubMed - in process] (Source: Haematologica)

Transcriptomic rationale for the synergy observed with dasatinib + bortezomib + dexamethasone in multiple myeloma

Abstract&nbsp;&nbsp;Despite the advantage observed with novel drugs such as bortezomib, thalidomide, or lenalidomide, multiple myeloma (MM) remains incurable and there is a clear need for new drugs or combinations based on the pathogenetic mechanism of MM. One of the proposed mechanisms in MM pathogenesis is the involvement of kinase molecules in the growth and survival of myelomatous cells. In this study, we have explored the optimal combination for dasatinib, a tyrosine kinase inhibitor, in MM cells. A clear synergistic effect was observed with the triple combination of dasatinib with bortezomib and dexamethasone which was evident even in the presence of bone marrow microenvironment. Experiments performed on freshly isolated patients‚?? cells also demonstrated potentiation of respo...

Primary plasma cell leukemia in the era of new drugs: Has something changed?

Abstract: Primary plasma cell leukemia (PPCL) is a rare and aggressive variant of multiple myeloma. This disease is associated with a very poor prognosis, and unfortunately it has not significantly improved during the last three decades. Autologous stem cell transplantation is generally recommended in eligible patients, but survival in transplanted PPCL patients is significantly lower than that of multiple myeloma. Recent preliminary data indicate that new drugs, in particular lenalidomide and bortezomib, could significantly improve the clinical outcome of PPCL, increasing response rate and duration, as well as survival. In this review we report an updated literature analysis about the current therapeutic scenario of PPCL, with a particular focus on the use of novel agents. (Source: Critic...

Treatment by Lenalidomide in lower risk myelodysplastic syndrome with 5q deletion‚??The GFM experience

Abstract: We treated 95 RBC transfusion dependent lower risk MDS with del 5q with Lenalidomide (10mg/day, 3 weeks/4 weeks). Median age was 70.4, median interval from diagnosis 29 months. IPSS was low in 31% and intermediate-1 in 69% patients. Del 5q was isolated, with 1 additional and >1 additional abnormality in 79%, 14%, and 6% patients, respectively. 62 (65%) patients achieved transfusion independence (TI). The only significant factor predicting TI was baseline platelet count >150G/L and platelet decrease by at least 50% during the first weeks of treatment (p=0.001). Grade III‚??IV neutropenia and thrombocytopenia were seen in 74% and 37.9% of the cases, respectively, and 3 deaths were attributed to cytopenias. Eight (8%) patients developed deep venous thrombosis (DVT). Platelet decreas...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

The differential effect of lenalidomide monotherapy in patients with relapsed or refractory transformed non‚?źHodgkin lymphoma of distinct histological origin

SummaryTransformed lymphoma (TL) represents a heterogeneous group of lymphomas with an aggressive course and poor prognosis. We assessed the clinical benefit of single‚?źagent lenalidomide based on histological origin, including transformed follicular lymphoma (tFL) and transformed chronic lymphocytic leukaemia/small lymphocytic lymphoma (tCLL/SLL). Our analysis included 33 patients with TL. Patients received lenalidomide at a median dose of 25‚??mg/d. The overall response rate (ORR) was 46%, with a median response duration of 12¬∑8‚??months after a median follow‚?źup of 5¬∑6‚??months. Median progression‚?źfree survival was 5¬∑4‚??months. Among patients with tFL, ORR was 57%, with a median response duration of 12¬∑8‚??months. None of the patients with tCLL/SLL responded to lenalidomide mon...

Inflammation, TNFőĪ, and endothelial dysfunction link lenalidomide to venous thrombosis in chronic lymphocytic leukemia

AbstractPatients receiving lenalidomide are at an increased risk for deep venous thrombosis (DVT). Here, we prospectively investigated the DVT risk in patients with relapsed chronic lymphocytic leukemia treated with lenalidomide (n=32). Five patients developed six incidents of DVT over one year for an annual incidence of 16%. Three of these were considered drug‚?źrelated. Median time to DVT was 105 days (range 56‚?ź259 days). No pulmonary embolism was detected. Hypercoagulability screen before study entry was negative in all patients who subsequently developed DVTs. Compared to normal volunteers CLL patients had increased baseline levels of D‚?źdimer, thrombin‚?źantithrombin, soluble vascular endothelial adhesion molecule 1 (sVCAM‚?ź1), and thrombomodulin (P&lt;0.001). After one week on le...

[Comment] Multiple myeloma and the road to personalised medicine

Rapid advances in myeloma-cell genotyping and phenotyping are bringing personalised myeloma therapy ever closer. Since the introduction of thalidomide, lenalidomide, and bortezomib, treatment outcomes have improved overall, but there is still great variability between patients and little consensus about how best to use the new drugs with the older ones. The practising haematologist now has to choose between many induction, consolidation, and maintenance regimens that combine two, three, or all four active classes of drugs at varying doses, and for varying periods of time. (Source: The Lancet Oncology)

Inflammation, TNFőĪ and endothelial dysfunction link lenalidomide to venous thrombosis in chronic lymphocytic leukemia

AbstractPatients receiving lenalidomide are at an increased risk for deep venous thrombosis (DVT). Here, we prospectively investigated the DVT risk in patients with relapsed chronic lymphocytic leukemia (CLL) treated with lenalidomide (n = 32). Five patients developed six incidents of DVT over 1 year for an annual incidence of 16%. Three of these were considered drug‚?źrelated. Median time to DVT was 105 days (range 56‚??259 days). No pulmonary embolism was detected. Hypercoagulability screen before study entry was negative in all patients who subsequently developed DVTs. Compared to normal volunteers CLL patients had increased baseline levels of D‚?źdimer, thrombin‚?źantithrombin, soluble vascular endothelial adhesion molecule 1 (sVCAM‚?ź1), and thrombomodulin (p &lt; 0.001). After 1 week...

Lenalidomide downregulates the cell survival factor, interferon regulatory factor‚?ź4, providing a potential mechanistic link for predicting response

This study showed that lenalidomide downregulated IRF4 levels in MM cell lines and bone marrow samples within 8‚??h of drug exposure. This was associated with a decrease in MYC levels, as well as an initial G1 cell cycle arrest, decreased cell proliferation, and cell death by day‚??5 of treatment. In eight MM cell lines, high IRF4 levels correlated with increased lenalidomide sensitivity. The clinical significance of this observation was investigated in 154 patients with MM. Among MM patients with high levels of IRF4 expression, treatment with lenalidomide led to a significantly longer overall survival than other therapies in a retrospective analysis. These data confirm the central role of IRF4 in MM pathogenesis; indicate that this is an important mechanism by which lenalidomide exerts it...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Stevens‚??Johnson syndrome after lenalidomide therapy for multiple myeloma: a case report and a review of treatment options

AbstractStevens‚?ź Johnson syndrome (SJS) is a severe and life‚?źthreatening condition. Although allopurinol, an antihyperuricemia drug, is the drug most commonly associated with SJS, more than 100 different causative drugs have been reported. Among hematologic drugs recently introduced into the market, drugs such as rituximab, imatinib, and bortezomib are reported. Here, we describe a patient with SJS while receiving lenalidomide in combination with prednisolone for treatment‚?źna√Įve multiple myeloma. Although SJS has been reported rarely as an adverse reaction to Lenalidomide, this drug should be considered in the etiology of SJS, and the increased number of prescriptions of Lenalidomide for the therapy of multiple myeloma has to stress the awareness of its potentially serious side‚?źef...

An international phase II trial of single-agent lenalidomide for relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma

Conclusion: Lenalidomide is well tolerated and produces durable responses in patients with relapsed or refractory aggressive non-Hodgkin&rsquo;s lymphoma. (Source: Annals of Oncology)

Thalidomide, dexamethasone and lovastatin with autologous stem cell transplantation as a salvage immunomodulatory therapy in patients with relapsed and refractory multiple myeloma

Abstract&nbsp;&nbsp;The treatment of patients with multiple myeloma usually includes many drugs including thalidomide, lenalidomide and bortezomib. Lovastatin and other inhibitors of HMG-CoA reductase demonstrated to exhibit antineoplasmatic and proapoptotic properties in numerous in vitro studies involving myeloma cell lines. We treated 91 patients with relapsed or refractory multiple myeloma with thalidomide, dexamethasone and lovastatin (TDL group, 49 patients) or thalidomide and dexamethasone (TD group, 42 patients). A clinical response defined of at least 50% reduction of monoclonal band has been observed in 32% of TD patients and 44% of TDL patients. Prolongation of overall survival and progression-free survival in the TDL group as compared with the TD group has been documented...

GELA, The Premier Cooperative Group In Adult Lymphoma Research Choses REVLIMID(R) For Major Study In Follicular Lymphoma

Groupe d'Etude des Lymphomes de l'Adulte (GELA) and Celgene International Sarl (Nasdaq: CELG) today announced a collaboration to conduct an international randomized study to evaluate the therapeutic potential of the REVLIMID (lenalidomide)/rituximab combination regimen (R2) in patients with newly diagnosed follicular lymphoma (FL). The RELEVANCE Study (Rituximab and Lenalidomide vs. Any Chemotherapy) looks to advance the treatment of patients diagnosed with FL, a form of non-Hodgkin's lymphoma (NHL)... (Source: Health News from Medical News Today)

POEMS syndrome: 2011 update on diagnosis, risk‚?źstratification, and management

AbstractDisease overviewPOEMS syndrome is a paraneoplastic syndrome due to an underlying plasma cell neoplasm. The major criteria for the syndrome are polyradiculoneuropathy, clonal plasma cell disorder (PCD), sclerotic bone lesions, elevated vascular endothelial growth factor, and the presence of Castleman disease. Minor features include organomegaly, endocrinopathy, characteristic skin changes, papilledema, extravascular volume overload, and thrombocytosis. Diagnoses are often delayed because the syndrome is rare and can be mistaken for other neurologic disorders, most commonly chronic inflammatory demyelinating polyradiculoneuropathy. POEMS syndrome should be distinguished from the Castleman disease variant of POEMS syndrome, which has no clonal PCD and typically little to no peripheral...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Induction Chemotherapy With Revlimid Does Not Impair Stem Cell Collection

A study released in the June edition of&#160; Leukemia has shown that induction chemotherapy with lenalidomide, or Revlimid, does not prevent myeloma patients from collecting enough stem cells for a double or "tandem" stem cell transplant....Read Full Post (Source: About.com Lymphoma)

GELA, the Premier Cooperative Group in Adult Lymphoma Research Choses Revlimid for Major Study in Follicular Lymphoma

Celgene and GELA Announce Second Collaboration with the "RELEVANCE" Study Evaluating REVLIMID plus Rituximab for Patients Newly-Diagnosed with Follicular Lymphoma BOUDRY, Switzerland & LYON, France, Jun 17, 2011 (BUSINESS WIRE) -- roupe d'Etude... (Source: Drugs.com - Pharma News)

Lenalidomide can be highly effective in chronic lymphocytic leukaemia despite T‚?źcell depletion and deletion of chromosome 17p

SummaryLenalidomide is an immunomodulatory agent with activity in a range of haematological cancers including chronic lymphocytic leukaemia (CLL). However, major questions remain concerning its effectiveness in patients with T‚?źcell depletion or deletion of TP53 on chromosome 17p. This case report provides insight into these questions by showing that lenalidomide/dexamethasone in combination can be highly effective as induction therapy for refractory 17p‚?ź CLL, that remission quality can be improved by subsequent maintenance with lenalidomide alone, and that the anti‚?źleukemic effects of lenalidomide and its stimulatory effects on non‚?źmalignant B cells are preserved despite prolonged T‚?źcell depletion resulting from prior alemtuzumab/methylprednisolone. (Source: European Journal of H...

Rapid response of plasmacytomas to lenalidomide plus low‚?źdose dexamethasone therapy in a patient with relapsed multiple myeloma

(Source: American Journal of Hematology)

Lenalidomide: Various toxicities in an elderly patient: case report

(Source: Reactions)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

International Myeloma Working Group consensus approach to the treatment of multiple myeloma patients who are candidates for autologous stem cell transplantation

This article reviews the current literature and provides important perspectives and guidance on the major issues surrounding the optimal current management of younger, transplantation-eligible MM patients. (Source: Blood)

Haematological and cytogenetic responses after only 7 days of Lenalidomide in a patient with myelodysplastic syndrome and chromosome 5q deletion

We report a patient with lower risk MDS with 5q deletion who achieved RBC transfusion independence after only 7 days of LEN, during 8 months (Source: Leukemia Research)

Fatal ischemic stroke in a patient receiving lenalidomide for multiple myeloma

Lenalidomide is a novel treatment that significantly increases survival time in patients with relapsed or refractory multiple myeloma . Known side effects include neutropenia, thrombocytopenia and venous thromboembolism . (Source: Clinical Neurology and Neurosurgery)

Lenalidomide is active for extramedullary disease in refractory multiple myeloma

Content Type Journal ArticlePages 1-2DOI 10.1007/s00277-011-1272-6Authors Tomonori Nakazato, Department of Hematology, Yokohama Municipal Citizen‚??s Hospital, Yokohama, 56 Okazawa-cho, Hodogaya-ku, Yokohama, 240-8555 JapanAi Mihara, Department of Hematology, Yokohama Municipal Citizen‚??s Hospital, Yokohama, 56 Okazawa-cho, Hodogaya-ku, Yokohama, 240-8555 JapanChisako Ito, Department of Hematology, Yokohama Municipal Citizen‚??s Hospital, Yokohama, 56 Okazawa-cho, Hodogaya-ku, Yokohama, 240-8555 JapanYukinari Sanada, Department of Hematology, Yokohama Municipal Citizen‚??s Hospital, Yokohama, 56 Okazawa-cho, Hodogaya-ku, Yokohama, 240-8555 JapanYoshinobu Aisa, Department of Hematology, Yokohama Municipal Citizen‚??s Hospital, Yokohama, 56 Okazawa-cho, Hodogaya-ku, Yokohama, 240-8555 J...

Dexamethasone/lenalidomide: Various toxicities: 3 case reports

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Lenalidomide: Spontaneous haematoma (first report) and thrombocytopenia: case report

(Source: Reactions)

Stem cell mobilization in patients with newly diagnosed multiple myeloma after lenalidomide induction therapy

Authors: F Cavallo, S Bringhen, G Milone, D Ben-Yehuda, A Nagler, E Calabrese, N Cascavilla, V Montefusco, B Lupo, A M Liberati, C Crippa, F Rossini, R Passera, F Patriarca, A M Cafro, P Omed&#232;, A M Carella, J Peccatori, L Catalano, T Caravita, P Musto, M T Petrucci, M Boccadoro & A Palumbo (Source: Leukemia)

New agents in follicular lymphoma

The follicular lymphomas are indolent diseases that are highly responsive to various combinations of standard chemotherapy drugs. Nevertheless, until recently, no regimen had improved patient outcome. The incorporation of effective and well-tolerated monoclonal antibodies, such as rituximab, into chemoimmunotherapeutic strategies provided the first evidence that survival of these patients could be prolonged. Nevertheless, follicular lymphoma remains incurable and characterized by recurrent relapses requiring additional treatment. An increasing number of effective drugs are now being evaluated either alone or in combinations including the chemotherapy drugs bendamustine and bortezomib. More targeted agents include monoclonal antibodies and their derivatives such as drug-antibody conjugates ...

Molecular Target Characterization and Anti-myeloma Activity of the Novel, Insulin-like Growth Factor 1 Receptor Inhibitor, GTx-134.

CONCLUSIONS: These studies support the potential therapeutic efficacy of GTx-134 in MM. Further, they provide a rationale for clinical application in combination with established anti-myeloma treatments and novel targeted therapies. PMID: 21632854 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Stevens‚??Johnson syndrome after lenalidomide therapy for multiple myeloma: a case report and a review of treatment options

AbstractStevens‚?ź Johnson syndrome (SJS) is a severe and life‚?źthreatening condition. Although allopurinol, an antihyperuricemia drug, is the drug most commonly associated with SJS, more than 100 different causative drugs have been reported. Among hematologic drugs recently introduced into the market, drugs such as rituximab, imatinib, and bortezomib are reported. Here, we describe a patient with SJS while receiving lenalidomide in combination with prednisolone for treatment‚?źna√Įve multiple myeloma. Although SJS has been reported rarely as an adverse reaction to Lenalidomide, this drug should be considered in the etiology of SJS, and the increased number of prescriptions of Lenalidomide for the therapy of multiple myeloma has to stress the awareness of its potentially serious side‚?źef...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Very short-term lenalidomide treatment associated with durable resolution of anemia in a patient with myelodysplastic syndrome with chromosome 5q deletion

Content Type Journal ArticlePages 1-2DOI 10.1007/s00277-011-1263-7Authors Laura Cannella, Department of Cellular Biotechnology and Hematology, Sapienza University of Rome, Via Benevento, 6, 00161 Roma, ItalyRoberto Latagliata, Department of Cellular Biotechnology and Hematology, Sapienza University of Rome, Via Benevento, 6, 00161 Roma, ItalyMassimo Breccia, Department of Cellular Biotechnology and Hematology, Sapienza University of Rome, Via Benevento, 6, 00161 Roma, ItalyIda Carmosino, Department of Cellular Biotechnology and Hematology, Sapienza University of Rome, Via Benevento, 6, 00161 Roma, ItalyGiuseppina Loglisci, Department of Cellular Biotechnology and Hematology, Sapienza University of Rome, Via Benevento, 6, 00161 Roma, ItalyPaola Volpicelli, Department of Cellular Biotech...

The B lineage transcription factor E2A regulates apoptosis in chronic lymphocytic leukemia (CLL) cells

Chronic lymphocytic leukemia (CLL) is a common malignancy characterized by the accumulation of B lymphocytes with an antigen-experienced activated CD19+CD5+ clonal phenotype. Clinically, ~50% of cases will behave more aggressively. Here, we investigate the role of the major B-cell transcription factor E2A, a known regulator of B-cell survival and proliferation, to CLL persistence. We show that E2A is elevated at the mRNA and protein levels relative to normal B-cell subsets. E2A silencing in primary CLL cells leads to a significant increase in spontaneous apoptosis in both CD38+ (aggressive) and CD38&ndash; (indolent) cases. Moreover, E2A knockdown synergizes with the immunomodulatory drug lenalidomide to reduce CLL viability. E2A is known to restrain the proliferation of primary B and T ly...

Stick to licensed indications for lenalidomide

(Source: Reactions)

Lenalidomide Maintenance Improves Overall Survival in Multiple Myeloma

Treatment with lenalidomide after stem cell transplantation shows a survival benefit in the latest update of the Cancer and Leukemia Group phase 3 trial. Medscape Medical News (Source: Medscape Today Headlines)

Hematology: Allografting offers better outcomes than autografting for patients with myeloma

Nature Reviews Clinical Oncology 8, 386 (2011). doi:10.1038/nrclinonc.2011.78 Author: Lisa Hutchinson For the treatment of young patients with myeloma, autologous transplantation has been regarded the standard of care. While the introduction of newer agents, such as lenalidomide and bortezomib, have dramatically changed the treatment landscape for this disease, allografting is still considered the only means of (Source: Nature Clinical Practice Oncology)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Design, synthesis and biological assessment of novel N-substituted 3-(phthalimidin-2-yl)-2,6-dioxopiperidines and 3-substituted 2,6-dioxopiperidines for TNF-őĪ inhibitory activity.

Authors: Luo W, Yu QS, Salcedo I, Holloway HW, Lahiri DK, Brossi A, Tweedie D, Greig NH Eight novel 2-(2,6-dioxopiperidin-3-yl)phthalimidine EM-12 dithiocarbamates 9 and 10, N-substituted 3-(phthalimidin-2-yl)-2,6-dioxopiperidines 11-14 and 3-substituted 2,6-dioxopiperidines 16and 18were synthesized as tumor necrosis factor-őĪ (TNF-őĪ) synthesis inhibitors. Synthesis involved utilization of a novel condensation approach, a one-pot reaction involving addition, iminium rearrangement and elimination, to generate the phthalimidine ring required for the creation of compounds 9-14. Agents were, thereafter, quantitatively assessed for their ability to suppress the synthesis on TNF-őĪ in a lipopolysaccharide (LPS)-challenged mouse macrophage-like cellular screen, utilizing cultured RAW 264.7 c...

Myelodysplastic syndromes: 2011 update on diagnosis, risk‚?źstratification, and management

AbstractDisease overview:The myelodysplastic (MDS) are a very heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increased risk of transformation to acute myelogenous leukemia (AML). MDS occurs more frequently in older male and in individuals with prior exposure to cytotoxic therapy.Diagnosis:Diagnosis of MDS is based on morphological evidence of dysplasia upon visual examination of a bone marrow aspirate and biopsy. Information obtained from additional studies such as karyotype, flow cytometry, or molecular genetics is complementary but not diagnostic.Risk‚?źstratification:Prognosis of patients with MDS can be calculated using a number of scoring systems. In general, all these scoring systems include analysis of peripheral cytopenias, percentage of b...

TP53 Mutations in Low-Risk Myelodysplastic Syndromes With del(5q) Predict Disease Progression [Hematologic Malignancies]

Conclusion By using sensitive deep-sequencing technology, we demonstrated that TP53 mutated populations may occur at an early disease stage in almost a fifth of low-risk MDS patients with del(5q). Importantly, mutations were present years before disease progression and were associated with an increased risk of leukemic evolution. TP53 mutations could not be predicted by common clinical features but were associated with p53 overexpression. Our findings indicate a previously unrecognized heterogeneity of the disease which may significantly affect clinical decision making. (Source: Journal of Clinical Oncology)

Diffuse alveolar hemorrhage associated with lenalidomide.

Authors: Sakai M, Kubota T, Kuwayama Y, Ikezoe T, Yokoyama A PMID: 21573890 [PubMed - as supplied by publisher] (Source: International Journal of Hematology)

Treatment With Lenalidomide After Stem-Cell Transplant Improves Multiple Myeloma Survival, Reduces Risk Of Progression

Updated data from a National Cancer Institute-sponsored clinical trial conducted by the Cancer and Leukemia Group (CALGB) was presented May 5 at the 13th International Myeloma Workshop in Paris, France. The phase III study evaluated the benefits of continuous, or maintenance, treatment with lenalidomide (Revlimid) following an autologous stem-cell transplant in newly diagnosed multiple myeloma patients and found that lenalidomide delays time to disease progression and improves overall survival compared to placebo... (Source: Health News from Medical News Today)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

REVLIMID (Lenalidomide) Capsule [Celgene Corporation]

Updated Date: May 12, 2011 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

IMiD immunomodulatory compounds block C/EBP{beta} translation through eIF4E down-regulation resulting in inhibition of MM

Immunomodulatory derivatives of thalidomide (IMiD compounds), such as pomalidomide and lenalidomide, are highly active in multiple myeloma (MM) treatment. However, the precise mechanisms of action and resistance in MM are unresolved. Here we show that IMiD compounds down-regulate CCAAT/enhancer-binding protein-&beta; (C/EBP&beta;) resulting in abrogation of cell proliferation. Overexpression of C/EBP&beta; rescued MM cells from IMiD-induced inhibition of proliferation, indicating that C/EBP&beta; is critical in mediating antiproliferative effects. IMiD-induced decrease of C/EBP&beta; protein led to impaired transcription of interferon regulatory factor 4 (IRF4). Down-regulation of IRF4 by lenalidomide was confirmed by longitudinal studies of bone marrow samples from 23 patients obtained be...

Lenalidomide: Erythema multiforme and Sweet's syndrome: case report

(Source: Reactions)

MHRA Drug Safety Update: Review of benefits and risks of lenalidomide

Source: MHRA Drug Safety Update Area: Evidence > Medication Safety The May 2011 issue of Drug Safety Update from the MHRA reminds healthcare professionals that the European Medicines Agency (EMA) is reviewing the benefit/risk balance of lenalidomide (Revlimid¬ģ), following reports of a possible link to an increased risk of second primary malignancies in patients treated in clinical studies conducted outside of the licensed indication. &nbsp; Three Phase III clinical studies are evaluating lenalidomide in the first-line treatment of multiple myeloma (it is currently only licensed for use in combination with dexamethasone for those who have received at least one prior treatment).&nbsp; Data from these studies (summarised in the report - see link below) show an apparent excess of second ...

A prospective clinical trial of lenalidomide with topotecan in women with advanced epithelial ovarian carcinoma

Conclusion&nbsp;&nbsp;The addition of lenalidomide to topotecan is not a feasible drug combination in women with advanced epithelial ovarian carcinoma because of dose-limiting toxicity. Content Type Journal ArticlePages 1-5DOI 10.1007/s10147-011-0243-1Authors Jori S. Carter, Department of Obstetrics, Gynecology, and Women‚??s Health, University of Minnesota, 420 Delaware Street SE, MMC 395, Minneapolis, MN 55455, USALevi S. Downs, Department of Obstetrics, Gynecology, and Women‚??s Health, University of Minnesota, 420 Delaware Street SE, MMC 395, Minneapolis, MN 55455, USA Journal International Journal of Clinical OncologyOnline ISSN 1437-7772Print ISSN 1341-9625 (Source: International Journal of Clinical Oncology)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Continuous Lenalidomide Boosts Overall Survival In Multiple Myeloma Patients

PARIS - Lenalidomide (Revlimid¬ģ) used continuously after autologous stem cell transplant (ASCT) significantly improves overall survival in patients with multiple myeloma, according to results released at the 13th International Myeloma Workshop. The data are from an update of the National Cancer Institute-sponsored Cancer and Leukemia Group B (CALGB) 100104 study. Patients who received continuous oral lenalidomide had a median overall survival rate of 90% (208/231) versus 83% (190/229) for placebo-treated patients at a median follow-up of 28 months (p=0.018)... (Source: Health News from Medical News Today)

Lenalidomide is effective for extramedullary disease in relapsed or refractory multiple myeloma

(Source: European Journal of Haematology)

Multiple Phase III Studies Confirm Statistically Significant Clinical Benefit Of Continuous REVLIMID Treatment For Patients With Multiple Myeloma At International Myeloma Workshop

Celgene International Sàrl today announced data from multiple phase III studies evaluating the benefit/risk profile of REVLIMID were presented during the International Myeloma Workshop in Paris, France. (Source: Pharmaceutical Online News)

Unexpected Erythroid and Cytogenetic Responses After Discontinuation of a Short Course of Lenalidomide As a Result of Severe Skin Rash in a Patient With 5q Syndrome [DIAGNOSIS IN ONCOLOGY]

(Source: Journal of Clinical Oncology)

Current Trends in Autologous Stem-Cell Transplantation for Myeloma in the Era of Novel Therapies [REVIEW ARTICLES]

Since the mid 1990s, high-dose therapy followed by autologous stem-cell transplantation (ASCT) has been considered the standard of care for frontline therapy in younger patients with multiple myeloma (MM). During the past 10 years, thalidomide, bortezomib, and lenalidomide have been widely incorporated to the therapeutic armamentarium for the treatment of this disease. These agents show promise for improving the rate of complete remission both before and after ASCT without increasing toxicity. However, it is not clear whether such therapies are superior if they are used as an alternative to transplantation or whether they may reduce the need for and use of transplantation in patients in whom treatment is indicated. Therefore, the role of ASCT itself is a matter of debate: Should it be used...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Celgene Stock Falls On Worries About Secondary Cancers

Shares of Celgene, the biotech industry&#8217;s largest standalone maker of cancer drugs, fell 3.45% to $58.84 as new data reinforced worries that long-term use of its top-seller Revlimid to treat the blood cancer multiple myeloma actually increases the number of secondary cancers even as it extends patients&#8217; lives. (Source: Forbes.com Healthcare News)

Celgene's Revlimid extends life in cancer trial

BOSTON (Reuters) - Celgene Corp said on Thursday that data from a clinical trial of its blood cancer drug Revlimid showed it significantly extended survival in patients who received the drug as maintenance therapy following a stem cell transplant. (Source: Reuters: Health)

Long-term maintenance treatment demonstrates 90% overall survival rate

U.S. Study of Continuous REVLIMID? Therapy following Transplant Validates Important Treatment Option for Patients (Source: International Myeloma Foundation)

Long-term Maintenance Tx Demonstrates 90% Overall Survival Rate

U.S. Study of Continuous REVLIMID? Therapy following Transplant Validates Important Treatment Option for Patients (Source: International Myeloma Foundation)

Revlimid (lenalidomide) extends life in multiple myeloma trial

BOSTON (Reuters) - Celgene Corp's cancer drug Revlimid (lenalidomide) significantly extended the lives of patients with multiple myeloma who took the drug as a maintenance therapy following a stem cell transplant. (Source: Modern Medicine)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Salvage therapy with lenalidomide and dexamethasone in patients with advanced AL amyloidosis refractory to melphalan, bortezomib, and thalidomide

Abstract&nbsp;&nbsp;The increasing number of effective agents allows rescue therapy of patients with light-chain (AL) amyloidosis refractory to ‚?•2 previous treatments. Lenalidomide is effective in this disease and its toxicity profile encourages its use in salvage regimens. All the patients with AL amyloidosis refractory to both melphalan and bortezomib referred to our center between July 2007 and July 2009 were treated with the combination of lenalidomide and dexamethasone. Twenty-four consecutive patients were enrolled. Seventy-nine percent were also refractory to thalidomide. Two patients died before evaluation of response, and 50% experienced severe adverse events. Survival was significantly shorter in subjects with troponin I &gt;0.1&nbsp;ng/mL and in patients diagnosed &lt;18...

Multiple Myeloma

series:Recent Results in Cancer ResearchMultiple myeloma is currently still an incurable disease, but during the past decade knowledge of its molecular pathogenesis has increased rapidly. This has led to remarkable progress in both diagnosis and therapy. In particular, the approval of novel and first-in-class drugs such as thalidomide, bortezomib, and lenalidomide means that multiple myeloma now stands at the forefront of advances ... (Source: Springer Medicine titles)

Lenalidomide targets clonogenic side population in multiple myeloma: pathophysiologic and clinical implications

Recurrence of multiple myeloma (MM) after therapy suggests the presence of tumor-initiating subpopulations. In our study, we performed flow cytometry&ndash;based Hoechst 33342 staining to evaluate the existence of a MM population with stem-like features known as side population (SP) cells. SP cells exhibit substantial heterogeneity in MM cell lines and primary MM cells; express CD138 antigen in MM cell lines; display higher mRNA expression and functional activity of ABCG2 transporter; and have a higher proliferation index compared with non-SP cells. We observed evidence for clonogenic potential of SP cells, as well as the ability of SP cells to regenerate original population. Moreover, SP cells revealed higher tumorigenicity compared with non-SP cells. Importantly, lenalidomide decreased t...

Will New Focus on Lenalidomide Risks Reveal More About Its Benefits?

Studies appear to suggest that the risk of progression to leukemia is increased in MDS patients who take lenalidomide. But as progression occurs in 10% of untreated patients, it has been difficult to establish whether the apparent increase with lenalidomide is the result of patient selection issues. (Source: Cancer Network)

Waldenström macroglobulinemia: 2011 update on diagnosis, risk stratification, and management

AbstractDisease overview: Waldenstr√∂m macroglobulinemia (WM) is a lymphoplasmacytic lymphoma with immunoglobulin M (IgM) monoclonal protein. Clinical features include anemia, thrombocytopenia, hepatosplenomegaly, and lymphadenopathy. Diagnosis: Presence of IgM monoclonal protein associated with ‚?•10% clonal lymphoplasmacytic cells in bone marrow confirms the diagnosis. Risk stratification: Age, hemoglobin level, platelet count, ő≤2‚?źmicroglobulin, and monoclonal IgM concentrations are characteristics required for prognosis. Risk adapted therapy: Not all patients who fulfill WM criteria require therapy; these patients can be observed until symptoms develop. Rituximab‚?źbased therapy is used in virtually all US patients with WM and can be combined with alkylating agent or purine nucleosid...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

A small molecule, LLL12 inhibits constitutive STAT3 and IL‚?ź6‚?źinduced STAT3 signaling and exhibits potent growth suppressive activity in human multiple myeloma cells

AbstractWe characterized the effects of a newly developed STAT3 inhibitor, LLL12 in multiple myeloma (MM) cells. LLL12 specifically inhibited STAT3 phosphorylation, nuclear localization, DNA binding activity‚?°down‚?źregulated STAT3 downstream genes, and induced apoptosis in MM cells. Importantly, LLL12 significantly inhibited STAT3 phosphorylation, induced apoptosis in primary MM cells which came from patients that were clinically resistant to lenalidomide and bortezomib. LLL12 is a potent inhibitor of cell proliferation with IC50 values ranging between 0.26őľM and 1.96őľM in MM and primary MM cells. LLL12 also inhibited STAT3 phosphorylation induced by interleukin‚?ź6 (IL‚?ź6) and interferon‚?źőĪ but not STAT1, STAT2, STAT4, and STAT6 phosphorylation induced by interferon‚?źőĪ, interfero...

[New insights in the treatment of myeloma with renal failure.]

Authors: Moumas E, Hanf W, Desport E, Abraham J, Delbès S, Debiais C, Lacotte-Thierry L, Touchard G, Jaccard A, Fermand JP, Bridoux F Renal failure, mostly related to myeloma cast nephropathy (MCN), is a frequent complication of multiple myeloma (MM), which occurs in up to 50% of patients during the course of the disease. Persistent renal failure in MM is associated with poor survival. Treatment of MCN relies on urgent symptomatic measures (alkalinisation, rehydration, correction of hypercalcemia, and withdrawal of nephrotoxic drugs), with rapid introduction of chemotherapy to efficiently reduce the production of monoclonal light chains (LC). Recent studies suggest that, in patients with MM and severe renal failure due to MCN, rapid removal of circulating LC, through intensive hemodia...

The role of phosphatidylinositol 3-kinase-{delta} in the immunomodulatory effects of lenalidomide in chronic lymphocytic leukemia

In patients with chronic lymphocytic leukemia (CLL), lenalidomide can promote humoral immune responses but also induces a distinct disease-specific toxicity of tumor flare and cytokine release. These CLL-specific events result from increased expression of costimulatory molecules on B cells. Here we demonstrate that lenalidomide activation of CLL cells depends on the phosphatidylinositol 3-kinase p110 (PI3K-) pathway. Inhibition of PI3K- signaling by the PI3K--inhibiting drug, CAL-101, or by siRNA knockdown of p110, abrogates CLL cell activation, costimulatory molecule expression, and vascular endothelial growth factor and basic fibroblast growth factor gene expression that is induced by lenalidomide. In addition, CAL-101 attenuates lenalidomide-mediated increases in immunoglobulin M produc...

Lenalidomide, cyclophosphamide and dexamethasone (CRd) for newly diagnosed multiple myeloma: Results from a phase 2 trial

AbstractThe combination of lenalidomide and low‚?źdose dexamethasone is an effective treatment for multiple myeloma (MM). Addition of alkylating agents to lenalidomide or thalidomide results in increased response rates and deeper responses. We designed this trial to study the combination of cyclophosphamide, lenalidomide and dexamethasone (CRd) as initial therapy for MM. Fifty‚?źthree patients with previously untreated symptomatic MM were enrolled. Patients received 4‚?źweek treatment cycles consisting of lenalidomide (25 mg daily for 3 weeks), dexamethasone (40 mg weekly) and cyclophosphamide (300 mg/m2 weekly for 3 weeks). A partial response or better was seen in 85% of patients including 47% with a very good partial response or better. The toxicities were manageable with over 80% of pla...

Practical management of adverse events in multiple myeloma: Can therapy be attenuated in older patients?

This article will provide practical guidance on the management of bortezomib-, thalidomide-, and lenalidomide-associated AEs, to maximize treatment feasibility and active drug delivered, and thus help minimize toxicity and maximize outcomes. (Source: Blood Reviews)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

FDA warns Revlimid linked to new malignancies

(Source: Reactions)

Stevens‚??Johnson/toxic epidermal necrolysis overlap syndrome following lenalidomide treatment for multiple myeloma relapse after allogeneic transplantation

Content Type Journal ArticlePages 1-3DOI 10.1007/s00277-011-1235-yAuthors Ralph W√§sch, Department of Hematology, Oncology and Stem Cell Transplantation, University Medical Center, Freiburg, GermanyThilo Jakob, Department of Dermatology, University Medical Center, Freiburg, GermanyKristin Technau, Department of Dermatology, University Medical Center, Freiburg, GermanyJ√ľrgen Finke, Department of Hematology, Oncology and Stem Cell Transplantation, University Medical Center, Freiburg, GermanyMonika Engelhardt, Department of Hematology, Oncology and Stem Cell Transplantation, University Medical Center, Freiburg, Germany Journal Annals of HematologyOnline ISSN 1432-0584Print ISSN 0939-5555 (Source: Annals of Hematology)

Higher response to lenalidomide in relapsed/refractory diffuse large b‚?źcell lymphoma in nongerminal center b‚?źcell‚??like than in germinal center b‚?źcell‚??like phenotype

CONCLUSIONS:The data suggest that the 2 major subgroups of patients with DLBCL (germinal center B cell and nongerminal center B cell) have different antitumor responsiveness to lenalidomide in the relapsed/refractory setting. A large international trial (NCT01197560) has been opened to enrollment in an attempt to prospectively validate these retrospective observations. Cancer 2011;. © 2011 American Cancer Society. (Source: Cancer)

[Current treatment of AL amyloidosis.]

Authors: Desport E, Moumas E, Abraham J, Delbès S, Lacotte-Thierry L, Touchard G, Fermand JP, Bridoux F, Jaccard A Systemic AL amyloidosis is a rare complication of monoclonal gammopathies. Renal manifestations are frequent, mostly characterized by heavy proteinuria, with nephrotic syndrome and renal failure in more than half of the patients at diagnosis. Without treatment, median survival does not exceed 12 months. Amyloid heart disease and diffusion of amyloid deposits are associated with reduced survival. Treatment of systemic AL amyloidosis has been profoundly modified with the introduction of international criteria for the definition of organ involvement and hematologic response, and with the use of sensitive tests for the measurement of serum-free light chain levels. Melphalan p...

Dexamethasone/lenalidomide: Transient inflammatory reaction: 2 case reports

(Source: Reactions)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Lenalidomide - Current Understanding of Mechanistic Properties

(Source: Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents))

A Case of Drug-Induced Hepatitis due to Lenalidomide

Case Rep Gastroenterol 2011;5:217‚??222 (DOI:10.1159/000326935) (Source: Karger Publishers)

FDA Investigating Cancer Risk With Lenalidomide

Lenalidomide (Revlimid) may be associated with an increased risk for certain forms of hematologic malignancies, according to the FDA. Medscape Medical News (Source: Medscape Today Headlines)

FDA conducts ongoing review of lenalidomide

(Source: HemOncToday.com)

FDA Drug Safety Communication: Ongoing Safety Review of Revlimid (lenalidomide) and Possible Increased Risk of Developing New Malignancies

Safety Announcement Additional Information for Patients Additional Information for Healthcare Professionals Data Summary Safety Announcement   [04-08-2011] The U.S. Food and Drug Administration (FDA) is informing the public that we... (Source: Drugs.com - Pharma News)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

FDA communication: Ongoing safety review of lenalidomide and increased risk of developing new malignancies

Source: FDA Area: News The FDA is informing the public that it is aware of results from clinical trials that found patients treated with lenalidomide may be at an increased risk of developing new types of cancer compared to patients who did not take the drug. The Agency is currently reviewing all available information on this potential risk and will communicate any new recommendations once it has completed its review. In the meantime, it has stated that there is no recommendation to delay, modify or restrict the use of this drug for patients being treated according to approved indications. (Source: NeLM - News)

Lenalidomide May Up Risk of Developing New Cancers

The U.S. Food and Drug Administration has notified health care providers that lenalidomide (Revlimid) appears to be associated with an increased risk of developing new types of cancer. (Source: Modern Medicine)

Revlimid (lenalidomide): Ongoing Safety Review - Increased Risk of Developing New Malignancies

Patients may be at an increased risk of developing new types of cancer compared to patients who did not take the drug. (Source: FDA MedWatch)

Efficacy of thalidomide- or lenalidomide-based therapy in proliferative multiple myeloma

Authors: P Kapoor, S Kumar, S J Mandrekar, K M Laumann, A Dispenzieri, M Q Lacy, D Dingli, M A Gertz, R A Kyle, P R Greipp, S V Rajkumar & T E Witzig (Source: Leukemia)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Dexamethasone/lenalidomide: Neutropenia in an elderly patient: case report

(Source: Reactions)

Lenalidomide: A Review of its Use in the Treatment of Relapsed or Refractory Multiple Myeloma

(Source: Drugs)

[Comment] New combinations for mantle cell lymphoma: concerted action needed

Mantle cell lymphoma is one of the most difficult to treat subtypes of non-Hodgkin lymphoma; most patients ultimately die from the disease. Although, progress has been made‚??eg, optimised first-line therapies resulting in long-term remissions‚??the response of patients to subsequent traditional therapies is often disappointing. New hope came with the introduction of novel agents into the treatment of mantle cell lymphoma: therapeutic advances have been achieved in trials of bortezomib, lenalidomide, and temsirolimus, which proved that these drugs all have single-agent activity in advanced disease. (Source: The Lancet Oncology)

Multiple Myeloma, Venous Thromboembolism, and Treatment-Related Risk of Thrombosis

Semin Thromb Hemost 2011; 37: 209-219DOI: 10.1055/s-0031-1273085ABSTRACTVenous thromboembolism (VTE) is a disease with a high prevalence in elderly people, affecting &gt; 5% of the population &gt; 65 years of age. Cancer patients have a 4.3-fold higher incidence of thrombotic complications, due to multiple risk factors that are not always related to the disease. Among hematologic malignancies, multiple myeloma (MM) confers a high risk of developing such complications, with a VTE rate of nearly 10%. Multiple factors are involved in MM-related VTE, such as increased blood viscosity, high levels of immunoglobulin, procoagulant activity of monoclonal protein, and inflammatory cytokines. Since the introduction of the immunomodulatory derivatives (IMiDs) thalidomide and lenalidomide in the thera...

Transformation of the 5q- syndrome to acute lymphoblastic leukemia: a report of two cases and review of the literature.

We present two cases of 5q- syndrome with a similar and unusual course of transformation to lymphoblastic leukemia while on Lenalidomide. These two patients achieved an initial response; however, later acquired a second cytogenetic abnormality, became refractory to treatment and evolved into acute leukemia. At the time of transformation, both patients had recurrence of the 5q- abnormality. Review of the literature and the mechanisms of transformation of the 5q-syndrome into an acute leukemia are discussed. Although the relationship between the events in our cases remains unclear, the intriguing similarity between the two cases raises a question whether immune modulators can alter the natural course of MDS. To our knowledge, no similar cases were previously reported in the literature. P...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Multiple Myeloma Treatment Strategies with Novel Agents in 2011: A European Perspective.

Authors: Ludwig H, Beksac M, Bladé J, Cavenagh J, Cavo M, Delforge M, Dimopoulos M, Drach J, Einsele H, Facon T, Goldschmidt H, Harousseau JL, Hess U, Kropff M, Leal da Costa F, Louw V, Magen-Nativ H, Mendeleeva L, Nahi H, Plesner T, San-Miguel J, Sonneveld P, Udvardy M, Sondergeld P, Palumbo A Abstract The arrival of the novel agents thalidomide, bortezomib, and lenalidomide has significantly changed our approach to the management of multiple myeloma and, importantly, patient outcomes have improved. These agents have been investigated intensively in different treatment settings, providing us with data to make evidence-based decisions regarding the optimal management of patients. This review is an update to a previous summary of European treatment practices that examines new data that...

Management of Lower-Risk Myelodysplastic Syndromes:The Art and Evidence

Abstract&nbsp;&nbsp;Myelodysplastic syndromes (MDS) represent a spectrum of bone marrow failure with variable outcome. Patients with ‚??lower-risk‚?Ě disease have an expected median survival measured in years, and a low risk of leukemia progression. Patients with ‚??higher-risk‚?Ě MDS, on the other hand, have expected survival measured in months without treatment and rapid leukemia progression. The outcome of those distinct groups can be explained by different underlying disease biology. In clinical practice, patients are stratified into risk groups based on prognostic models, most commonly the International Prognostic Scoring System (IPSS). In higher-risk disease, the standard of care is hypomethylating agents to extend survival and suppress leukemia potential, and consideration of ...

Identification of prognostic factors for plerixafor‚?źbased hematopoietic stem cell mobilization

AbstractThe introduction of plerixafor has enabled successful collection of stem cells in the majority of patients with lymphoma or myeloma in whom previous attempts at mobilization have failed. However, a proportion of patients have been shown to be resistant to this mobilization regimen. To identify the factors that impair stem cell mobilization and collection with plerixafor, we reviewed the data for 197 patients who had undergone mobilization with plerixafor and granulocyte‚?źcolony stimulating factor in Central Europe. Predictors of mobilization failure were evaluated using logistic regression analysis. Among the 197 patients mobilized, the target of ‚?• 2.0√?106 CD34+ cells/kg was collected from 133 (67.5%). Our analysis revealed that previous treatment with lenalidomide, bortezomib,...

{beta}-Catenin Signaling Mediates Lenalidomide Resistance [Cell Biology]

Lenalidomide plays an important role in our chemotherapeutic armamentarium against multiple myeloma, in part by exerting direct anti-proliferative and pro-apoptotic effects. Unfortunately, long-term exposure leads to the development of drug resistance through unknown mechanisms, and we therefore sought to identify pathways that could be responsible for this phenotype. Chronic drug exposure produced myeloma cell lines that were tolerant of the direct effects of lenalidomide, with a degree of resistance of up to 2,500-fold. Gene expression profiling and pathway analysis identified dysregulation of the Wnt/ő≤-catenin pathway as a consistent change across four independent cell isolates, and a pair of primary plasma cell samples. Acute drug treatment also increased ő≤-catenin transcription by 3...

Spontaneous Autologous Graft-versus-Host Disease in Plasma Cell Myeloma Autograft Recipients: Flow Cytometric Analysis of Hematopoietic Progenitor Cell Grafts

Nine plasma cell myeloma patients spontaneously developed histologically proven autologous graft-versus-host disease (GVHD) limited predominantly to the gastrointestinal tract within 1 month of initial autologous hematopoietic cell transplantation (AHCT) using high-dose melphalan conditioning. All recipients responded promptly to systemic and nonabsorbable oral corticosteroid therapy. All patients previously received systemic therapy with thalidomide, lenalidomide, or bortezomib before AHCT. Using enzymatic amplification staining-enhanced flow cytometry, we evaluated expression of selected transcription regulators, pathway molecules, and surface receptors on samples of the infused hematopoietic cell grafts. We demonstrated significantly enhanced expression of GATA-2, CD130, and CXCR4 on CD...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Anti-myeloma activity of a multi targeted kinase inhibitor, AT9283, via potent Aurora Kinase and STAT3 inhibition either alone or in combination with lenalidomide.

CONCLUSIONS: Demonstration of in vitro and in vivo anti-MM activity of AT9283 provides the rationale for clinical evaluation of AT9283 as monotherapy and in combination in patients with MM. PMID: 21430070 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Hematology: Setting the standard for newly diagnosed multiple myeloma

Authors: Jacob Laubach, Paul G. Richardson & Kenneth Anderson The treatment of multiple myeloma has evolved rapidly with the use of the immunomodulatory agents thalidomide and lenalidomide as well as the proteasome inhibitor bortezomib. Cavo and colleagues recently reported results of a landmark phase III study comparing thalidomide&#8211;dexamethasone with bortezomib&#8211;thalidomide&#8211;dexamethasone in newly diagnosed multiple myeloma. (Source: Nature Clinical Practice Oncology)

Myelodysplastic Syndrome Presenting as Generalized Granulomatous Dermatitis [Observation]

Conclusions&nbsp; There is a paucity of literature documenting the occurrence of granulomatous dermatitis as a manifestation of an underlying hematologic disorder. This case illustrates a striking example of widespread granulomatous dermatitis heralding the onset of MDS. It is imperative that the dermatologic community recognize the rare association of granulomatous dermatitis with myelodysplasia, because the cutaneous manifestations may be the presenting finding and can precede the development of leukemia by several years. (Source: Archives of Dermatology)

Gastrointestinal relapse of multiple myeloma and sustained response to lenalidomide: a case report

Conclusions: Clinicians must consider digestive tract involvement in myeloma patients presenting with a gastrointestinal hemorrhage. Furthermore, myeloma patients do benefit from novel oral drugs, even when they are critically ill. (Source: BioMed Central)

European CHMP begins review of lenalidomide (Revlimid) and possible link to second primary malignancies

Source: European Medicines Agency (EMA) Area: News The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has started a review of the benefit-risk balance of lenalidomide (Revlimid), following reports of a possible link to an increased risk of second primary malignancies in patients treated in clinical studies conducted outside of the licensed indication. The Committee will now review all available data to assess their impact on the balance of risks and benefits of this drug in its licensed indication. While the review is ongoing, the Committee is not recommending a delay, modification or restriction in the use of lenalidomide for patients treated according to the product license. (Source: NeLM - News)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Single-Agent Lenalidomide in the Treatment of Previously Untreated Chronic Lymphocytic Leukemia [Hematologic Malignancies]

Conclusion Lenalidomide is clinically active as first-line CLL therapy and is well-tolerated if a conservative approach with slow dose escalation is used. A lenalidomide-induced molecular signature provides insights into its immunomodulatory mechanisms of action in CLL. (Source: Journal of Clinical Oncology)

Recent advances in myeloma treatment

Abstract: The novel agents including thalidomide, bortezomib and lenalidomide have been incorporated into combination regimens which are moving from the advanced/refractory setting to first-line treatment. For the majority of elderly patients, the following regimens are considered standard: melphalan+prednisone in combination with bortezomib or thalidomide and the combination of lenalidomide+low-dose dex. For transplant-eligible patients novel agents are included in the induction phase before and in the consolidation/maintenance phase after transplant. In the relapsed/refractory setting, combinations of novel agents generate the best results but cumulative toxicity is limiting. Several newer agents such as carfilzomib, pomalidomide and deacetylase inhibitors are entering phase II and III c...

The Role of Bortezomib, Thalidomide and Lenalidomide in the Management of Multiple Myeloma: An Overview of Clinical and Economic Information

(Source: PharmacoEconomics)

Treatment of Newly Diagnosed Multiple Myeloma in Transplant-Eligible Patients

Abstract&nbsp;&nbsp;Treatment of myeloma has changed significantly in the past decade as a result of better understanding of disease biology, more effective treatments, and improved supportive care. Autologous stem cell transplantation (SCT) is an effective treatment for myeloma and remains a critical component in its management. Given the potential impact of therapy on stem cell collection, initial treatment decisions in myeloma still depend on the patient‚??s transplant eligibility. The goals of initial therapy remain rapid disease control allowing for reversal of disease complications, as well as reduction in the risk of early death‚??all with minimal toxicity. The introduction of new drugs such as thalidomide, bortezomib, and lenalidomide has enabled us to achieve this goal, and ...

Polycythemia vera evolving into a rapidly progressive Ph-negative del(5q)-positive myeloproliferative neoplasm refractory to lenalidomide

We report herein a unique case of a patient with polycythemia vera that transformed into an aggressive and rapidly fatal MPN with 5q- abnormality, unresponsive to low-dose lenalidomide. (Source: Leukemia Research)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Sudden acute leukemia transformation in a MDS patient with del(5q) in complete cytogenetic remission after lenalidomide

High proportion of del(5q) myelodysplastic (MDS) patients achieves transfusion independence and complete cytogenetic remission following treatment with lenalidomide, a thalidomide analogue with anti-angiogenetic, immunomodulating and cytotoxic effects . Lenalidomide was approved in 2005 by FDA for the treatment of MDS patients with del(5q), but little is known about the long-term outcome of these patients. Recently, Gohring et al. reported the follow-up of 42 patients treated with lenalidomide for a median period of 40 months: 36% of them progressed to acute leukemia (AML) with 87% showing clonal cytogenetic evolution in addition to del(5q). However, patients who had obtained erythroid and/or cytogenetic responses displayed a significantly decreased risk of progression at 5 years compared ...

Erratum to: pegylated liposomal doxorubicin in combination with dexamethasone and bortezomib (VMD) or lenalidomide (RMD) in multiple myeloma pretreated patients

Content Type Journal ArticlePages 1-1DOI 10.1007/s00277-011-1203-6Authors Gabriele Buda, Department of Oncology, Transplants and Advanced Technologies, Section of Hematology, Pisa University, Via Roma 67, 56100 Pisa, ItalyEnrico Orciuolo, Department of Oncology, Transplants and Advanced Technologies, Section of Hematology, Pisa University, Via Roma 67, 56100 Pisa, ItalySara Galimberti, Department of Oncology, Transplants and Advanced Technologies, Section of Hematology, Pisa University, Via Roma 67, 56100 Pisa, ItalyMatteo Pelosini, Department of Oncology, Transplants and Advanced Technologies, Section of Hematology, Pisa University, Via Roma 67, 56100 Pisa, ItalyMario Petrini, Department of Oncology, Transplants and Advanced Technologies, Section of Hematology, Pisa University, Via Ro...

Information sent to healthcare professionals in February 2011 about the safety of medicines

Source: MHRA Area: News The following letters were sent to healthcare professionals in February 2011, to inform of new safety information and advice. &nbsp; .&nbsp;Lenalidomide: association with venous and arterial thromboembolic events &nbsp; .&nbsp;Modafinil: new information to support safer use for treatment of adults with excessive sleepiness &nbsp; .&nbsp;Thyrotropin alfa (Thyrogen): error in the indication information provided in two recent communications (Source: NeLM - Mental Health)

Lenalidomide is effective as salvage therapy in refractory or relapsed multiple myeloma: analysis of the Spanish Compassionate Use Registry in advanced patients.

Authors: Alegre A, Aguado B, Giraldo P, R√≠os E, C√°novas A, Ib√°√Īez A, Castillo I, Hern√°ndez MT, Oriol A, Palomera L, Rodr√≠guez JN, Garc√≠a FL, Calvo JM, Mart√≠nez-Chamorro C, de la Serna J, Lahuerta JJ We evaluated the clinical results of lenalidomide (Len) as a compassionate salvage therapy in refractory/relapsed multiple myeloma (MM) patients. A nationwide multi-centre, retrospective research study was performed to evaluate clinical data from patients with advanced MM for which compassionate use of lenalidomide was requested. The primary endpoints were the overall response rate (ORR) and the time to progression (TTP). Secondary objectives included safety and overall survival (OS) since starting of lenalidomide therapy. Data collected from the Spanish Compassionate Use Registry i...

Dermatological complications following initiation of lenalidomide in a patient with chronic lymphocytic leukaemia

We present an unusual case of CLL that was complicated by erythema annulare centrifugum and neutrophilic dermatosis (Sweet's syndrome) after starting Len. (Source: Internal Medicine Journal)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

A review of the history, properties, and use of the immunomodulatory compound lenalidomide

Lenalidomide (REVLIMID‚?Ę), an immunomodulatory compound targeting both cancer cells and their microenvironment, has substantial activity in several difficult‚?źto‚?źmanage hematological malignancies. In previously treated multiple myeloma, lenalidomide produces high‚?źquality responses combined with sustained disease control. Recently, several randomized studies have demonstrated a clinical benefit of continuous lenalidomide treatment in newly diagnosed multiple myeloma. In many patients with refractory anemia associated with lower risk myelodysplastic syndromes and a 5q chromosome deletion, lenalidomide leads to transfusion independence, considerably improving quality of life. It has a manageable safety profile, and its oral formulation reduces the burden on patients. Several phase III t...

Impact of response to thalidomide-, lenalidomide- or bortezomib- containing induction therapy on the outcomes of multiple myeloma patients undergoing autologous transplantation

Authors: F T Awan, S Osman, S T Kochuparambil, L Gibson, S C Remick, J Abraham, M Craig, A Jillella & M Hamadani (Source: Bone Marrow Transplantation)

Initial testing of lenalidomide by the pediatric preclinical testing program

ConclusionsDirect antiproliferative effects of lenalidomide were not observed in vitro. In vivo lenalidomide demonstrated low activity against tumors in immune‚?źdeficient mice. Our results suggest that lenalidomide's utility in the pediatric clinical setting may depend upon its ability to induce antitumor activity through effects on host immune and stromal cells rather than through direct effects on tumor cells. Pediatr Blood Cancer ¬© 2011 Wiley‚?źLiss, Inc. (Source: Pediatric Blood and Cancer)

Treatment with lenalidomide modulates T‚?źcell immunophenotype and cytokine production in patients with chronic lymphocytic leukemia

CONCLUSIONS:Treatment with lenalidomide resulted in the normalization of functional T‚?źcell subsets in responders, suggesting that lenalidomide may modulate cell‚?źmediated immunity in patients with CLL. Cancer 2011;. ¬© 2011 American Cancer Society. (Source: Cancer)

Treatment of Newly Diagnosed Myeloma in Patients not Eligible for Transplantation

Abstract&nbsp;&nbsp;Melphalan plus prednisone (MP) has long been considered the gold-standard treatment for elderly patients with newly diagnosed myeloma, and it still forms the backbone for combinations based on novel agents. MP plus thalidomide (MPT), bortezomib (VMP), or lenalidomide (MPR), as induction plus maintenance, have proved to be superior to MP and are currently the treatment of choice for this population. Low-dose dexamethasone in combination with thalidomide and cyclophosphamide (CTDa) or with lenalidomide can be an alternative option for these patients. The benefit of these novel agents in terms of prolonged survival is accompanied by increases in treatment-related adverse events, however, which may be particularly pronounced in older individuals. In managing these pat...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Kidney dysfunction during lenalidomide treatment for AL amyloidosis

Conclusions. Among patients with AL amyloidosis, worsening of kidney function occurs frequently during lenalidomide treatment. While a causal role of the drug has not been established, our findings suggest that kidney function should be monitored closely during treatment with this drug. (Source: Nephrology Dialysis Transplantation)

Previous thalidomide therapy may not affect lenalidomide response and outcome in relapse or refractory multiple myeloma patients

Conclusion: Lenalidomide may be equally effective in heavily pre-treated multiple myeloma patients who are thalidomide-resistant or thalidomide-sensitive to a previous therapy. (Source: European Journal of Cancer)

Lenalidomide and omalizumab linked to thrombotic events

(Source: Reactions)

New Immunomodulatory Drugs in Myeloma

Abstract&nbsp;&nbsp;Multiple myeloma (MM) is an incurable malignancy of plasma cells. The introduction of thalidomide was a milestone in the treatment of MM. Thalidomide analogues termed immunomodulatory drugs (IMiDs) have been developed that are more effective and have less toxicity than thalidomide. The role of lenalidomide in relapsed MM has been well defined. This review discusses the data regarding the upfront use of lenalidomide with dexamethasone or in multidrug combinations, as well as its potential role as maintenance therapy. It also reviews our experience with pomalidomide, a new IMid with remarkable activity in relapsed, refractory MM. Content Type Journal ArticlePages 1-6DOI 10.1007/s11899-011-0077-yAuthors Martha Q. Lacy, Division of Hematology, Mayo Clinic, 200 Fi...

Revlimid (lenalidomide) -Revised SPC

Source: eMC (electronic Medicines Compendium) Area: Other Library Updates > SPC Changes Section 4.2 of the SPC has been updated and now states "Prescribing physicians should carefully evaluate which dose of dexamethasone to use, taking into account the condition and disease status of the patient." at the end of the Recommended Dose section. &nbsp; Additional information&nbsp;in section 4.4 of the SPC has been added under "Cardiovascular disorders", regarding Myocardial Infarction and Venous and Arterial Thromboembolic Events. Please refer to SPC for detailed information. &nbsp; Section 4.8 has been amended to include adverse reactions noted from post marketing data. &nbsp; Please see link to SPC below for full prescribing information. (Source: NeLM - SPC Changes)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Thyroid abnormalities in patients treated with lenalidomide for hematological malignancies: Results of a retrospective case review

(Source: American Journal of Hematology)

MHRA Drug Safety Update (February 2011): Lenalidomide: risk of thrombosis and thromboembolism

Source: MHRA Area: Evidence > Medication Safety The February issue of the Drug Safety Update from the MHRA contains a reminder that patients receiving lenalidomide for the management of multiple myeloma should be closely monitored for evidence of arterial and venous thromboembolic events. &nbsp; The following advice has been issued to healthcare professionals: &nbsp; .&nbsp;Patients receiving lenalidomide for the management of multiple myeloma should be closely monitored for evidence of arterial and venous thromboembolic events. &nbsp; .&nbsp;Modifiable risk factors for thromboembolic events should be managed wherever possible (e.g. smoking cessation; control of hypertension and hyperlipidaemia) &nbsp; .&nbsp;Medicines that may increase the risk of thromboembolism, such as...

A phase 2 study of high-dose lenalidomide as initial therapy for older patients with acute myeloid leukemia

This study is registered at www.clinicaltrials.gov as #NCT00546897. (Source: Blood)

Lenalidomide restrains motility and overangiogenic potential of bone marrow endothelial cells in patients with active multiple myeloma.

CONCLUSIONS: This study provides information on the molecular mechanisms associated with the antimigratory and antiangiogenic effects of lenalidomide in primary MMECs, thus giving new avenues for effective endothelium-targeted therapies in MM. PMID: 21307145 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Hypomethylating Agents and Other Novel Strategies in Myelodysplastic Syndromes [REVIEW ARTICLES]

Over the last decade, treatment approaches for patients with myelodysplastic syndromes (MDS) have improved significantly. Treatment of MDS is tailored to the specific risk characteristics of the patient. In general, patients are divided into lower- and higher-risk categories. Without therapy, prognosis of patients with higher-risk MDS is poor, and treatments should be directed to improve survival. Prognosis of patients with lower-risk MDS is more heterogeneous, and therapies are usually directed to minimize transfusion needs and potentially to alter the natural course of the disease. Treatment options for patients with higher-risk MDS include hypomethylating agents (azacitidine and decitabine), intensive chemotherapy (ICT), and allogeneic stem-cell transplantation (alloSCT). The use of the...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Management of older patients with multiple myeloma

Abstract: For many years, the oral combination melphalan‚??prednisone (MP) has been considered the standard of care for patients with multiple myeloma (MM) not eligible for autologous stem cell transplantation. In the era of novel agents, the introduction of immunomodulatory drugs and proteasome inhibitors has challenged the role of MP and led to new standards of care for this disease. Five randomized phase III studies compared the traditional MP with the MP plus thalidomide (MPT). All these studies showed a prolonged time to progression (TTP) with the 3-drug combination. However, in only two of these trials this advantage translated into an improvement in overall survival (OS). In another randomized trial, MP plus bortezomib (VMP) was correlated with an increase in both TTP and OS compare...

Optimizing the use of lenalidomide in relapsed or refractory multiple myeloma: consensus statement

Authors: M A Dimopoulos, A Palumbo, M Attal, M Beksa&#231;, F E Davies, M Delforge, H Einsele, R Hajek, J-L Harousseau, F Leal da Costa, H Ludwig, U-H Mellqvist, G J Morgan, J F San-Miguel, S Zweegman & P Sonneveld (Source: Leukemia)

The immunostimulatory effect of lenalidomide on NK-cell function is profoundly inhibited by concurrent dexamethasone therapy

Lenalidomide combined with dexamethasone is an effective treatment for refractory/relapsed multiple myeloma (MM). Lenalidomide stimulates natural killer (NK) cells and enhances antitumor responses. We assessed NK cell number and function in 25 patients with MM participating in a clinical trial of lenalidomide and dexamethasone. NK cell numbers increased from a mean of 2.20 &plusmn; 0.05 x 105/mL (baseline) to a mean of 3.90 &plusmn; 0.03 x 105/mL (cycle 6; P = .05); however, in vitro NK-cell&ndash;mediated cytotoxicity decreased from 48.9% &plusmn; 6.8% to 27.6% &plusmn; 5.1% (P = .0028) and could not be rescued by lenalidomide retreatment. Lenalidomide increased normal donor NK-cell cytotoxicity in vitro from 38.5% to 53.3%, but this was completely abrogated by dexamethasone. Dexamethason...

Transient inflammatory reaction during lenalidomide plus reduced-dose dexamethasone therapy in two patients with relapsed multiple myeloma.

Authors: Ozaki S, Harada T, Fujii S, Nakamura S, Miki H, Nakano A, Kagawa K, Takeuchi K, Abe M, Matsumoto T PMID: 21279817 [PubMed - as supplied by publisher] (Source: International Journal of Hematology)

US FDA grants fast track designation to carfilzomib for multiple myeloma

Source: BioSpace Area: News According to BioSpace, the US FDA has granted fast track designation to carfilzomib, a next generation proteasome inhibitor, for the potential treatment of patients with relapsed and refractory multiple myeloma. &nbsp; Positive results from a Phase IIb study (003-A1) study evaluating carfilzomib monotherapy in patients with relapsed and refractory multiple myeloma were recently announced at the American Society of Hematology (ASH) meeting in December 2010.&nbsp; Based on these results, the company has initiated a rolling submission of a New Drug Application (NDA) for potential accelerated approval of carfilzomib in the US.&nbsp; Carfilzomib was granted orphan drug designation by the FDA for the treatment of multiple myeloma in 2008. &nbsp; The carfilzom...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Design, synthesis and biological evaluation of new thalidomide analogues as TNF-őĪ and IL-6 production inhibitors.

Authors: Chaulet C, Croix C, Alagille D, Normand S, Delwail A, Favot L, Lecron JC, Viaud-Massuard MC Several thalidomide analogues were synthesized and compared to thalidomide and its more active analogue, lenalidomide, for their ability to inhibit the production of the pro-inflammatory cytokine tumour necrosis factor (TNF)-őĪ and interleukin (IL)-6 by LPS-activated peripheral blood mononuclear cells (PBMCs). Among these compounds, two analogues containing sulfonyl group displayed interesting downregulation of TNF-őĪ and IL-6 production. PMID: 21215621 [PubMed - in process] (Source: Bioorganic and Medicinal Chemistry Letters)

Immunoglobulin light chain amyloidosis: 2011 update on diagnosis, risk‚?źstratification, and management

AbstractImmunoglobulin (Ig) light chain amyloidosis is a clonal but nonproliferative plasma cell disorder in which fragments of an Ig light chain are deposited in tissues. The clinical features depend on the organs involved but can include restrictive cardiomyopathy, nephrotic syndrome, hepatic failure, and peripheral/autonomic neuropathy. Tissue biopsy stained with Congo red demonstrating amyloid deposits with apple‚?źgreen birefringence is required for diagnosis. Invasive organ biopsy is not required because amyloid deposits can be found in bone marrow biopsy or subcutaneous fat aspirate in 85% of patients. N‚?źterminal pro‚??brain natriuretic peptide and serum troponin T values are used to classify patients into three groups of approximately equal size; median survivals are 26.4, 10.5, ...

Rates of Venous Thromboembolism in Multiple Myeloma Patients Undergoing Immunomodulatory Therapy with Thalidomide or Lenalidomide: A Systematic Review and Meta‚?źAnalysis

Conclusion: Patients with newly diagnosed or previously treated MM receiving thalidomide‚?ź or lenalidomide‚?źbased regimens in combination with dexamethasone are at high risk of VTE. The benefit of various thromboprophylaxis is difficult to quantify in patients with MM receiving immunomodulatory therapy, especially in those receiving lenalidomide‚?źbased therapy or have previously treated MM. Randomized controlled trials are needed to address this important clinical need. (Source: Journal of Thrombosis and Haemostasis)

Safety, Pharmacokinetics, and Immunomodulatory Effects of Lenalidomide in Children and Adolescents With Relapsed/Refractory Solid Tumors or Myelodysplastic Syndrome: A Children's Oncology Group Phase I Consortium Report [Pediatric Oncology]

Conclusion Lenalidomide is well-tolerated at doses up to 70 mg/m2/d for 21 days in children with solid tumors. Drug clearance in children younger than 12 years is faster than in adolescents and young adults. Lenalidomide significantly upregulates cellular immunity, including NK and LAK activity. (Source: Journal of Clinical Oncology)

Phase I Trial of Lenalidomide in Pediatric Patients With Recurrent, Refractory, or Progressive Primary CNS Tumors: Pediatric Brain Tumor Consortium Study PBTC-018 [Pediatric Oncology]

Conclusion Lenalidomide was tolerable in children with CNS tumors at doses of 116 mg/m2/d during the initial dose-finding period. The primary toxicity is myelosuppression. Antitumor activity, defined by both objective responses and long-term stable disease, was observed, primarily in patients with low-grade gliomas. (Source: Journal of Clinical Oncology)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Clinical Spectrum, Treatment, and Outcome of Patients with Type II Mixed Cryoglobulinemia without Evidence of Hepatitis C Infection.

CONCLUSION: An important proportion of non HCV-related type II MC remains essential. Efforts should be made to find other etiologies than HCV, because treatments with steroid and immunosuppressants are not satisfactory, especially in severe forms. In these situations anti-CD20 therapy may present the best option but should be used with caution. New agents such as lenalidomide remain to be evaluated. PMID: 21239761 [PubMed - as supplied by publisher] (Source: J Rheumatol)

Lenalidomide: Acute interstitial nephritis: case report

(Source: Reactions)

Lenalidomide in the treatment of chronic lymphocytic leukemia

Expert Opinion on Investigational Drugs, Volume 0, Issue 0, Page 1-14, Early Online. (Source: Expert Opinion: Expert Opinion on Investigational Drugs: Table of Contents)

Mantle cell lymphoma: biology, pathogenesis, and the molecular basis of treatment in the genomic era

Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma of which at least a subset arises from antigen-experienced B cells. However, what role antigen stimulation plays in its pathogenesis remains ill defined. The genetic hallmark is the chromosomal translocation t(11;14) resulting in aberrant expression of cyclin D1. Secondary genetic events increase the oncogenic potential of cyclin D1 and frequently inactivate DNA damage response pathways. In combination these changes drive cell-cycle progression and give rise to pronounced genetic instability. Several signaling pathways contribute to MCL pathogenesis, including the often constitutively activated PI3K/AKT/mTOR pathway, which promotes tumor proliferation and survival. WNT, Hedgehog, and NF-B pathways also appear to be important. Alth...

Celgene Provides Update on Regulatory Submissions

REVLIMID(R) (lenalidomide) Capsules Marketing Authorisation Application Submitted to EMA for Treatment of Newly Diagnosed Multiple Myeloma And Maintenance Therapy ISTODAX(R) (romidepsin) for Injection Supplemental New Drug Application Submitted to... (Source: Drugs.com - Pharma News)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Celgene Seeks Approval for Blood Cancer Treatments

From Associated Press (January 4, 2011) Celgene Corp. said Tuesday it submitted for approval blood cancer treatments Revlimid and Istodax to European and U.S. regulators, respectively. The Summit, N.J., company is seeking approval for Revlimid... (Source: Drugs.com - Pharma News)

Hypercoagulability in Multiple Myeloma and Its Precursor State, Monoclonal Gammopathy of Undetermined Significance

Patients with multiple myeloma are at an increased risk of venous thromboembolism (VTE), especially when treated with the immunomodulatory drugs, thalidomide and lenalidomide, in combination with dexamethasone and/or chemotherapy. Several studies have shown that patients with multiple myeloma precursor disease (monoclonal gammopathy of undetermined significance [MGUS]) also have a higher risk of thrombosis compared to the general population. The underlying mechanisms for the hypercoagulable state are not completely understood. In this review, we discuss risk factors for thrombosis in multiple myeloma, as well as prophylactic strategies, the evidence for thrombosis among patients with MGUS, and proposed mechanisms for the hypercoagulability. (Source: Seminars in Hematology)

Conservative Lenalidomide Treatment Effective for CLL

The oral immunomodulatory drug lenalidomide appears to be clinically active and well tolerated as a first-line, single-agent treatment for chronic lymphocytic leukemia if given conservatively, according to research published online Dec. 28 in the Journal of Clinical Oncology. (Source: Modern Medicine)

Big Biotechs With The Most Upside for 2011 (AMGN, GILD, CELG, HGSI, DNDN, INCY, ACOR)

Bioheath Investor is creating some ongoing outlook pieces as 2010 ends so we have an outline of what to expect for 2011.  We have already given the &#8220;Best of Big Biotech in 2010&#8243; and now we want to focus on &#8220;The Big Biotechs With The Most Upside for 2011.&#8221;  Using &#8220;Big Biotech&#8221; implies market caps of those with a market cap of $1 billion or higher.  It was surprising that many of those big biotechs are actually trading much higher than their projected price targets. Our screen generated 7 of the pack with implied upside of more than 15% for 2011.  Those making the screen were Amgen Inc. (NASDAQ: AMGN), Gilead Sciences, Inc. (NASDAQ: GILD), Celgene Corporation (NASDAQ: CELG), Human Genome Sciences, Inc. (NASDAQ: HGSI), Dendreon Corporation (NASDAQ: DNDN...

Multiple myeloma: 2011 update on diagnosis, risk‚?źstratification, and management

AbstractDisease overview:Multiple myeloma is malignant plasma‚?źcell disorder that accounts for ‚?ľ‚?ľ10% of all hematologic malignancies.Diagnosis:The diagnosis requires (1) 10% or more clonal plasma cells on bone marrow examination or a biopsy‚?źproven plasmacytoma plus (2) evidence of end‚?źorgan damage felt to be related to the underlying plasma cell disorder.Risk stratification:Patients with 17p deletion, t(4;14), t(14;16), t(14;20), and karyotypic deletion 13 or hypodiploidy are considered to have high‚?źrisk myeloma. All others are considered to have standard‚?źrisk disease.Risk‚?źadapted therapy:Standard‚?źrisk patients are treated with nonalkylator‚?źbased therapy such as lenalidomide plus low‚?źdose dexamethasone (Rd) followed by autologous stem‚?źcell transplantation (ASCT). If ...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Advances in the 5q- syndrome

The 5q&ndash; syndrome is the most distinct of all the myelodysplastic syndromes with a clear genotype/phenotype relationship. The significant progress made during recent years has been based on the determination of the commonly deleted region and the demonstration of haploinsufficiency for the ribosomal gene RPS14. The functional screening of all the genes in the commonly deleted region determined that RPS14 haploinsufficiency is the probable cause of the erythroid defect in the 5q&ndash; syndrome. A mouse model of the human 5q&ndash; syndrome has now been created by chromosomal engineering involving a large-scale deletion of the Cd74-Nid67 interval (containing RPS14). A variety of lines of evidence support the model of ribosomal deficiency causing p53 activation and defective erythropoie...

Lenalidomide and high-dose dexamethasone compared with dexamethasone as initial therapy for multiple myeloma: a randomized Southwest Oncology Group trial (S0232)

The Southwest Oncology Group conducted a randomized trial comparing lenalidomide (LEN) plus dexamethasone (DEX; n = 97) to placebo (PLC) plus DEX (n = 95) in newly diagnosed myeloma. Three 35-day induction cycles applied DEX 40 mg/day on days 1 to 4, 9 to 12, and 17 to 20 together with LEN 25 mg/day for 28 days or PLC. Monthly maintenance used DEX 40 mg/day on days 1 to 4 and 15 to 18 along with LEN 25 mg/day for 21 days or PLC. Crossover from PLC-DEX to LEN-DEX was encouraged on progression. One-year progression-free survival, overall response rate, and very good partial response rate were superior with LEN-DEX (78% vs 52%, P = .002; 78% vs 48%, P &lt; .001; 63% vs 16%, P &lt; .001), whereas 1-year overall survival was similar (94% vs 88%; P = .25). Toxicities were more pronounced with LE...

Pegylated liposomal doxorubicin in combination with dexamethasone and bortezomib (VMD) or lenalidomide (RMD) in multiple myeloma pretreated patients

Content Type Journal ArticleDOI 10.1007/s00277-010-1136-5Authors Gabriele Buda, Department of Oncology, Transplants and Advanced Technologies, Section of Hematology, Pisa University, Via Roma 67, 56100 Pisa, ItalyEnrico Orciuolo, Department of Oncology, Transplants and Advanced Technologies, Section of Hematology, Pisa University, Via Roma 67, 56100 Pisa, ItalySara Galimberti, Department of Oncology, Transplants and Advanced Technologies, Section of Hematology, Pisa University, Via Roma 67, 56100 Pisa, ItalyMatteo Pelosini, Department of Oncology, Transplants and Advanced Technologies, Section of Hematology, Pisa University, Via Roma 67, 56100 Pisa, ItalyMario Petrini, Department of Oncology, Transplants and Advanced Technologies, Section of Hematology, Pisa University, Via Roma 67, 56...

Lenalidomide: Myocarditis (first report) in an elderly patient: case report

(Source: Reactions)

Mantle cell lymphoma: The promise of new treatment options

Abstract: Though the expected overall survival (OS) for mantle cell lymphoma (MCL) has doubled in the last 30 years it is still in the range of only 4‚??5 years. Despite high response rates with current first-line treatments, most patients eventually relapse and become typically chemoresistant, leading to very poor outcome in the relapsed setting. Here, we summarize the clinical characteristics of MCL and frontline strategies used in MCL, and review a number of novel options that are currently being investigated in an effort to extend survival outcomes for this difficult-to-treat patient population. Among these novel options figure cytotoxics (bendamustine, cladribine), new biologicals/small molecules such as proteasome inhibitors (bortezomib 1st drug approved in the USA for MCL), mTOR inh...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Treatment of Patients with Multiple Myeloma: An Overview of Systematic Reviews.

The objective of this overview is to summarize all existing systematic reviews on treatments in multiple myeloma (MM), which accounts for 14% of new cases of hematological malignancies each year. Therefore, MEDLINE and the Cochrane Database of Systematic Reviews were systematically searched to identify systematic reviews of interventions. Data were extracted on patients, interventions, control and outcomes. Methodological quality of the systematic reviews was assessed using the AMSTAR assessment tool. Eleven systematic reviews on treatment of MM were included in the overview. Ten addressed seven unique questions and also performed a meta-analysis. One addressed 21 clinical questions related to treatment decisions in myeloma. The quality of systematic reviews varied. The results from the ov...

fountain of youth pill Lenalidomide drug that could give you longer healthier life

Tests have shown that tiny amounts of the drug lenalidomide massively boosted immune system chemicals, helping to ward off everything from bugs to tumours. (Source: the Mail online | Health)

Immunomodulatory drugs increase endothelial tissue factor expression in vitro

Conclusions: Our in vitro data support the hypothesis that THL and LEN induce a hypercoagulable state through increased endothelial TF expression. (Source: Thrombosis Research)

Interferon-alpha in the Treatment of Multiple Myeloma.

Authors: Khoo TL, Vangsted AJ, Gibson J Interferons are soluble proteins produced naturally by cells in response to viruses. It has both anti-proliferative and immunomodulating properties and is one of the first examples of a biological response modifier use to treat the haematological malignancy multiple myeloma. Interferon has been used in this clinical practice for over thirty years. However, despite considerable efforts, numerous clinical trials and two large meta-analysis, its exact role in the management of multiple myeloma still remains unclear. Its role in the treatment of multiple myeloma has been as a single induction agent, a co-induction agent with other chemotherapy regimens, and as maintenance therapy after conventional chemotherapy or complete remission after autologous ...

Conference report: Secondary malignancies in studies of lenalidomide for multiple myeloma

Source: MedPage Today Area: News According to data presented at the American Society of Haematology (ASH) meeting, use of lenalidomide (Revlimid¬ģ) for multiple myeloma may be associated with an excess of new cancers.&nbsp; Although the overall number of secondary malignancies was low (44 in over 800 patients), the results from three studies showed a consistent increased risk compared to other comparative treatments.&nbsp; &nbsp; Researchers presented findings on secondary malignancies from three randomised studies of lenalidomide in MM.&nbsp; The first study, conducted by the CALGB, compared lenalidomide to placebo as maintenance therapy following autologous stem cell transplantation in patients with stage I-III myeloma.&nbsp; Although lenalidomide was found to reduce the risk of pro...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Drug Combination Shows Promise For Newly Diagnosed Blood Cancer Patients

A new three-drug combination used to treat the blood cancer multiple myeloma may be effective as a front-line therapy for newly diagnosed patients, according to a study led by the University of Michigan Comprehensive Cancer Center. The drug combination includes a novel proteasome inhibitor called carfilzomib, combined with lenalidomide and low-dose dexamethasone. This is the first study to look at carfilzomib as a front-line treatment of patients with myeloma, a type of cancer that arises in the plasma cells... (Source: Health News from Medical News Today)

Bortezomib with thalidomide plus dexamethasone vs. thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after stem-cell transplantation in newly diagnosed multiple myeloma

Source: Lancet Area: News Thalidomide, bortezomib, and lenalidomide have advanced the treatment of multiple myeloma over the past decade. Thalidomide or bortezomib in combination with melphalan plus prednisone is first-line treatment for elderly patients who are not eligible for transplant, whilst in young patients eligible for transplant, novel agents have been incorporated into induction treatments to increase the rate of high-quality response before autologous stem-cell transplantation, and thereby improve outcomes after transplantation. The rate of complete response with the use of the thalidomide plus dexamethasone (TD) induction regimen has typically been less than 10%. Small studies have indicated that addition of bortezomib to TD (VTD) results in increased rates of high-quality re...

Addition of bortezomib to thalidomide plus dexamethasone in patients with newly diagnosed multiple myeloma undergoing stem-cell transplantation

Source: Lancet Area: News Thalidomide, bortezomib, and lenalidomide have advanced the treatment of multiple myeloma over the past decade. Thalidomide or bortezomib in combination with melphalan plus prednisone is first-line treatment for elderly patients who are not eligible for transplant, whilst in young patients eligible for transplant, novel agents have been incorporated into induction treatments to increase the rate of high-quality response before autologous stem-cell transplantation, and thereby improve outcomes after transplantation. The rate of complete response with the use of the thalidomide plus dexamethasone (TD) induction regimen has typically been less than 10%. Small studies have indicated that addition of bortezomib to TD (VTD) results in increased rates of high-quality re...

Encouraging Phase 2 Interim Data For Elotuzumab In Relapsed Multiple Myeloma Presented At 52nd American Society Of Hematology Annual Meeting

Abbott (NYSE: ABT) and Bristol-Myers Squibb Company (NYSE: BMY) announced interim results from the Phase 2 portion of a Phase 1b/2 open-label study which showed a high objective response rate (ORR) among patients with relapsed multiple myeloma who received elotuzumab plus lenalidomide and low-dose dexamethasone. ORR, the primary endpoint of the Phase 2 portion of the study, was defined as partial response or better and assessed using International Myeloma Working Group (IMWG) criteria... (Source: Health News from Medical News Today)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Horizon scanning: Phase III results for continued lenalidomide in newly diagnosed multiple myeloma

Source: BioSpace Area: News Results from the second interim analysis of a Phase III study evaluating continued lenalidomide for the treatment of patients ?65 years with newly diagnosed multiple myeloma (MM) have been presented at the American Society of Hematology (ASH) Annual Meeting. &nbsp; The study randomised 459 patients to treatment with lenalidomide in combination with melphalan and prednisone (MPR), followed by lenalidomide alone (MPR-R; n=152); MPR followed by placebo (MPR; n=153) or placebo, melphalan and prednisone, followed by placebo (MP) (n=154). &nbsp; After a median of 21 months of follow-up, the following results were reported: &nbsp; .&nbsp;MPR-R (i.e. continued lenalidomide) was associated with a higher overall response rate (77% vs. 50%, p&lt;0.001) and a h...

Watson Enters Partnership For Generic Revlimid

From Associated Press (December 7, 2010) NEW YORK -- Watson Pharmaceuticals Inc. said Tuesday it acquired the U.S. rights to a generic version of Celgene Corp.&rsquo;s billion-selling cancer drug Revlimid. Natco Pharma Ltd. is developing a generic... (Source: Drugs.com - Pharma News)

Watson Confirms Development Agreement With Natco For Generic Revlimid&reg;

Watson Pharmaceuticals, Inc. (NYSE: WPI) and Natco Pharma Limited (BSE: 524816) today confirmed an exclusive, U.S. development and license agreement, to develop and commercialize lenalidomide 5, 10, 15 and 25 mg tablets. (Source: Pharmaceutical Online News)

Chromosomal aberrations +1q21 and del(17p13) predict survival in patients with recurrent multiple myeloma treated with lenalidomide and dexamethasone

CONCLUSIONS:The results of the current study suggest that the prognostic significance of t(4;14) may be ameliorated or eliminated in patients treated with len/dex, whereas the presence of del(17p13) or +1q21 is still associated with a dismal OS. The presence of t(11;14) and del(13q14) as exclusive chromosomal aberrations indicates no impact on outcome. Because of its rarity in MM, a confirmation of the prognostic role of the t(14;16) aberration is still pending. Cancer 2010. © 2010 American Cancer Society. (Source: Cancer)

Phase II Data Suggest Lenalidomide Consolidation Improves Quality of Response Following Induction With Pentostatin, Cyclophosphamide, and Rituximab in Previously Untreated CLL

Capsule Summary - In this nonrandomized, prospective trial, lenalidomide consolidation following pentostatin, cyclophosphamide, and rituximab induction appeared to prolong the time to retreatment compared with a previous trial evaluating pentostatin, cyclophosphamide, and rituximab without lenalidomide. (Source: Clinical Care Options Oncology - Leukemia)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Managing the teratogenic risk of thalidomide and lenalidomide: an industry perspective

Expert Opinion on Drug Safety, Volume 0, Issue 0, Page 1-6, Early Online. (Source: Expert Opinion: Expert Opinion on Drug Safety: Table of Contents)

REVLIMID (Lenalidomide) Capsule [Celgene Corporation]

Updated Date: Dec 2, 2010 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

Lenalidomide in combination with melphalan and dexamethasone in patients with newly diagnosed AL amyloidosis: a multicenter phase 1/2 dose-escalation study

This study is registered at www.clinicaltrials.gov as NCT00621400. (Source: Blood)

A novel orally active proteasome inhibitor ONX 0912 triggers in vitro and in vivo cytotoxicity in multiple myeloma

Bortezomib therapy has proven successful for the treatment of relapsed, relapsed/refractory, and newly diagnosed multiple myeloma (MM). At present, bortezomib is available as an intravenous injection, and its prolonged treatment is associated with toxicity and development of drug resistance. Here we show that the novel proteasome inhibitor ONX 0912, a tripeptide epoxyketone, inhibits growth and induces apoptosis in MM cells resistant to conventional and bortezomib therapies. The anti-MM activity of ONX-0912 is associated with activation of caspase-8, caspase-9, caspase-3, and poly(ADP) ribose polymerase, as well as inhibition of migration of MM cells and angiogenesis. ONX 0912, like bortezomib, predominantly inhibits chymotrypsin-like activity of the proteasome and is distinct from bortezo...

Increases in B-type natriuretic peptide (BNP) during treatment with lenalidomide in AL amyloidosis

(Source: Blood)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Preferential enhancement of older human T cell cytokine generation, chemotaxis, proliferation and survival by lenalidomide.

Authors: Huang MC, Greig NH, Luo W, Tweedie D, Schwartz JB, Longo DL, Ferrucci L, Ershler WB, Goetzl EJ Lenalidomide, an analog of thalidomide, modified responses of stimulated T cells from healthy young (ages 21-40years) and old (‚?•age 65years) subjects. At 0.03őľM to 1őľM, lenalidomide enhanced generation of IL-2 and IFN-ő≥ by T cell receptor-stimulated T cells of young subjects up to respective maximum increases of 17-fold and three-fold, but at 0.3őľM and 1őľM suppressed IL-17 generation. The same concentrations of lenalidomide enhanced IL-2 and IFN-ő≥ generation by stimulated T cells of old subjects more, with greater respective maximal increases of up to 120-fold and six-fold, without suppressing IL-17 generation. Lenalidomide enhanced proliferation and suppressed apoptosis of s...

Myeloma: making sense of a complex blood cancer.

Authors: Kelly MB, Meenaghan T, Dowling M Myeloma is a challenging blood cancer characterized by bone destruction, hypercalcaemia, renal insufficiency and anaemia. Although myeloma remains incurable, recent advancements in treatments have resulted in significant improvements in morbidity. The use of immunomodulatory drugs-thalidomide, lenalidomide, pomalidomide (in clinical trials)-and the proteasome inhibitor, bortezomib, in conjunction with conventional chemotherapy and supportive therapies, have resulted in a significant shift in approaches to treatment and an improvement in patients' quality of life. Nurses must remain up-to-date with current treatments for myeloma and their related side-effects. In addition, nurses play a key role in the coordination of a multidisciplinary approac...

Three rearrangements of chromosome 5 in a patient with myelodysplastic syndrome: an atypical deletion 5q, a complex intrachromosomal rearrangement of chromosome 5, and a paracentric inversion of chromosome 5

We report the case of a 74-year-old man who sought care for de novo myelodysplastic syndrome (RAEB-1). Conventional cytogenetic techniques showed a karyotype with two different deletions of the long arm of chromosome 5 distributed in three clones: 46,XY,del(1)(p34),del(5)(q14q23)[2]/46,XY,del(1)(p34),del(5)(q14q34)[10]/46,idem,inv(5)(q?11q?34)[7]. Precise characterization of the breakpoints, delineation of the deleted regions, identification of the complex intrachromosomal rearrangement of chromosome 5, and sequential accumulation of chromosomal abnormalities were elucidated by several fluorescence in situ hybridization analyses. We also assessed the clinical, biological, and cytogenetic evolution under lenalidomide treatment and after its interruption. (Source: Cancer Genetics and Cytogen...

The DAC system and associations with multiple myeloma

Summary&nbsp;&nbsp;Despite the clear progress achieved in recent years in the treatment of MM, most patients eventually relapse and therefore novel therapeutic options are still necessary for these patients. In this regard, several drugs that target specific mechanisms of the tumor cells are currently being explored in the preclinical and clinical setting. This manuscripts offers a review of the rationale and current status of the antimyeloma activity of one of the most relevant examples of these targeted drugs: deacetylase inhibitors (DACi). Several studies have demonstrated the prooncogenic activity of deacetylases (DACs) through the targeting not only of histones but also of non histone proteins relevant to tumor progression, such as p53, E2F family members, Bcl-6, Hsp90, HIF-1őĪ ...

Tumor flare reaction associated with lenalidomide treatment in patients with chronic lymphocytic leukemia predicts clinical response

CONCLUSIONS:TFR is a unique immune‚?źmediated phenomenon noted with lenalidomide treatment only in patients with CLL that correlates with clinical response. It can be effectively managed with anti‚?źinflammatory agents. Cancer 2010. ¬© 2010 American Cancer Society. (Source: Cancer)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Patient With HIV-Associated Plasmablastic Lymphoma Responding to Bortezomib Alone and in Combination With Dexamethasone, Gemcitabine, Oxaliplatin, Cytarabine, and Pegfilgrastim Chemotherapy and Lenalidomide Alone [DIAGNOSIS IN ONCOLOGY]

(No abstract is available for this citation) (Source: Journal of Clinical Oncology)

Lenalidomide and prednisone for myelofibrosis: Eastern Cooperative Oncology Group (ECOG) phase 2 trial E4903

This study was registered at http://clinicaltrials.gov as NCT00227591. (Source: Blood)

Towards effective immunotherapy of myeloma: enhanced elimination of myeloma cells by combination of lenalidomide with the human CD38 monoclonal antibody daratumumab.

Conclusions. Our results indicate that powerful and complementary effects may be achieved by combining Lenalidomide and Daratumumab in clinical multiple myeloma management. PMID: 21109694 [PubMed - as supplied by publisher] (Source: Haematologica)

Cytogenetic follow-up by karyotyping and fluorescence in situ hybridization: implications for monitoring patients with myelodysplastic syndrome and deletion 5q treated with lenalidomide.

In conclusion, to optimize therapy control of myelodysplastic syndrome patients with del(5q) treated with lenalidomide and to identify cytogenetic non-response or progression as early as possible, fluorescence in situ hybridization alone is inadequate for evaluation. Karyotyping must be performed to optimally evaluate response.(clinicaltrials.gov identifier: NCT01099267 and NCT00179621). PMID: 21109690 [PubMed - as supplied by publisher] (Source: Haematologica)

State of the art treatment of chronic lymphocytic leukaemia

Abstract: The management of chronic lymphocytic leukaemia is currently undergoing profound changes. Several drugs like bendamustine, alemtuzumab and rituximab have recently been approved for CLL treatment by regulatory agencies. New and very promising compounds like lenalidomide, ofatumumab, GA101, flavopiridol, or ABT-263 are currently investigated in clinical trials and are likely to further enlarge the therapeutic armamentarium in the next years. Latest results show that chemoimmunotherapies like FCR (fludarabine, cyclophosphamide and rituximab) may improve the life expectancy of CLL patients. This new paradigm will modify the way of CLL management in a radical manner. Finally, the development of new biological markers that describe distinct forms of CLL allows to enter the era of perso...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Thalidomide after lenalidomide: a possible treatment regimen in relapse refractory multiple myeloma patients

(Source: British Journal of Haematology)

Dose Escalation of Lenalidomide in Relapsed or Refractory Acute Leukemias [Hematologic Malignancies]

Conclusion Lenalidomide was safely escalated to 50 mg daily for 21 days, every 4 weeks, and was active with relatively low toxicity in patients with relapsed/refractory AML. Remissions achieved after transplantation suggest a possible immunomodulatory effect of lenalidomide, and results provide enthusiasm for further studies in AML, either alone or in combination with conventional agents or other immunotherapies. (Source: Journal of Clinical Oncology)

Renal Impairment in Patients With Multiple Myeloma: A Consensus Statement on Behalf of the International Myeloma Working Group [REVIEW ARTICLE]

Renal impairment is a common complication of multiple myeloma (MM). The estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease formula is the recommended method for the assessment of renal function in patients with MM with stabilized serum creatinine. In acute renal injury, the RIFLE (risk, injury, failure, loss and end-stage kidney disease) and Acute Renal Injury Network criteria seem to be appropriate to define the severity of renal impairment. Novel criteria based on eGFR measurements are recommended for the definition of the reversibility of renal impairment. Rapid intervention to reverse renal dysfunction is critical for the management of these patients, especially for those with light chain cast nephropathy. Bortezomib with high-dose dexamethasone...

In vitro cytotoxicity of the novel antimyeloma agents perifosine, bortezomib and lenalidomide against different cell lines

Summary&nbsp;&nbsp;The novel AKT inhibitor perifosine, a synthetic alkylphospholipid, is currently being investigated in clinical trials for the treatment of different hematological and oncological malignancies. The in vitro cytotoxicity of perifosine, bortezomib and lenalidomide against 6 cell lines derived from hematological malignancies was investigated using trypan blue staining, flow cytometry-based detection of activated caspases, Annexin V assays, immunohistochemistry studies (KI-67 and caspase-3 staining) and the immature-myeloid-information (IMI) technique. Perifosine and bortezomib induced concentration- and time-dependent cytotoxicity in all cell lines tested. Perifosine together with bortezomib largely exerted additive or synergistic effects with combination indices rangi...

Clinical impact of chromosomal aberrations in multiple myeloma

AbstractChromosomal aberrations are frequently found in multiple myeloma cells and play a major role in patient outcome and management of the disease. The most important chromosomal aberrations associated with poor outcome are del(17p), t(4;14), t(14;16) and t(14;20). Others that may be associated with adverse prognosis include amp(1)(q21), del(1p32), del(13), del(8p21) and hypodiploidy. Many chromosomal aberrations have no or uncertain impact; for example, t(11;14), t(8;14) and hyperdiploidy. Attempts have been made to overcome the negative prognostic impact of chromosomal aberrations using autologous or allogeneic transplantation or new immunomodulatory drugs such as thalidomide, lenalidomide and the proteasome inhibitor bortezomib, but the results are controversial. Data suggest that al...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Clinical management of myelodysplastic syndromes: update of SIE, SIES, GITMO practice guidelines

Abstract: Since 2002, date of publication of the previous Italian Society of Haematology (SIE) practice guidelines for management of myelodysplastic syndromes (MDS), novel disease-modifying treatments have been introduced and the SIE commissioned an update.After a comprehensive review of the medical literature published since January 2001, the Expert Panel formulated recommendations for the management of adult and paediatric MDS, graded according to the available evidence.The major updates are: first-line hypomethylating agents in patients with INT2-high-risk disease; controlled use of first-line lenalidomide in low-INT1 risk transfusion-dependent patients with 5q deletion; deferasirox in low-INT1 patients with a relevant transfusional load; first-line high-dose ESA in low-INT1 patients wi...

The lower risk MDS patient at risk of rapid progression

Abstract: Most patients with myelodysplastic syndrome (MDS) are classified at diagnosis as having a low/INT-I or INT-II/high risk disease, based on the classical International Prognostic Scoring System (IPSS) criteria. The low/INT-I risk patients are usually managed mildly with supportive care, including red blood cell (RBC) transfusions, erythroid stimulating agents (ESAs), other cytokines (G-CSF, platelet stimulating agents), as well as thalidomide and lenalidomide. Some patients receive immunosuppressive therapy, and iron chelation is indicated in iron overloaded patients. Aggressive approach (hypomethylating agents, chemotherapy and stem cell transplantation) is usually not applied in such patients.Occasionally, we observe a ‚??low risk‚?Ě patient with rapid progression of disease and ...

Outcomes after induction chemotherapy in patients with acute myeloid leukemia arising from myelodysplastic syndrome

CONCLUSIONS:Prior treatment with hypomethylating agents or lenalidomide, poor risk cytogenetics, and longer time to transformation to AML are independent negative predictive factors for response and OS in patients with secondary AML after induction therapy. Cancer 2010. © 2010 American Cancer Society. (Source: Cancer)

ESHAP chemotherapy regimen associated to lenalidomide induces complete isotopic remission in Hodgkin‚??s lymphoma relapsing after autologous stem cell transplantation

Content Type Journal ArticleDOI 10.1007/s00277-010-1107-xAuthors A. Tempescul, Department of Clinical Haematology, Institute of Cancerology and Hematology, University Hospital Brest, 2 avenue Foch, 29609 Brest cedex, FranceJ. C. Ianotto, Department of Clinical Haematology, Institute of Cancerology and Hematology, University Hospital Brest, 2 avenue Foch, 29609 Brest cedex, FranceJ. R. Eveillard, Department of Clinical Haematology, Institute of Cancerology and Hematology, University Hospital Brest, 2 avenue Foch, 29609 Brest cedex, FranceG. Guillerm, Department of Clinical Haematology, Institute of Cancerology and Hematology, University Hospital Brest, 2 avenue Foch, 29609 Brest cedex, FranceC. Berthou, Department of Clinical Haematology, Institute of Cancerology and Hematology, Univers...

A phase-2 trial of low-dose pomalidomide in myelofibrosis

Authors: K H Begna, R A Mesa, A Pardanani, W J Hogan, M R Litzow, R F McClure & A Tefferi (Source: Leukemia)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

[Review] Treatment-related peripheral neuropathy in multiple myeloma: the challenge continues

Introduction of the proteasome inhibitor bortezomib and the immunomodulatory drugs thalidomide and lenalidomide has substantially improved outcomes for patients with multiple myeloma. As a result, these drugs have become cornerstones of current antimyeloma treatment regimens. However, after several years of clinical experience it has become apparent that peripheral neuropathy is the most common and potentially disabling non-haematological side-effect associated with thalidomide and bortezomib. Maximising treatment benefit while preserving quality of life therefore requires a careful balance between achieving optimum activity and minimising toxicity, including neuropathy, to further enhance efficacy. (Source: The Lancet Oncology)

Immunoglobulin light chain amyloidosis: 2011 update on diagnosis, prognosis, and treatment

AbstractDisease Overview:Immunoglobulin (Ig) light chain amyloidosis is a clonal but nonproliferative plasma cell disorder in which fragments of an Ig light chain are deposited in tissues. The clinical features depend on the organs involved but can include restrictive cardiomyopathy, nephrotic syndrome, hepatic failure, and peripheral/autonomic neuropathy.Diagnosis:Tissue biopsy stained with Congo red demonstrating amyloid deposits with apple‚?źgreen birefringence is required for diagnosis. Invasive organ biopsy is not required because amyloid deposits can be found in bone marrow biopsy or subcutaneous fat aspirate in 85% of patients.Prognosis:N‚?źterminal pro‚??brain natriuretic peptide and serum troponin T values are used to classify patients into 3 groups of approximately equal size; me...

Celgene Reports Record Third Quarter 2010 Operating and Financial Results

Record Third Quarter Results Driven By Share Gains Across Major Markets REVLIMID&reg; Third Quarter Global Net Product Sales Increased 43% Y/Y VIDAZA&reg; Third Quarter Global Net Product Sales Increased 37% Y/Y Non-GAAP Third Quarter Diluted... (Source: Drugs.com - Pharma News)

Immunomodulatory effects of lenalidomide and pomalidomide on interaction of tumor and bone marrow accessory cells in multiple myeloma

The bone marrow (BM) microenvironment consists of extracellular-matrix and the cellular compartment including immune cells. Multiple myeloma (MM) cell and BM accessory cell interaction promotes MM survival via both cell-cell contact and cytokines. Immunomodulatory agents (IMiDs) target not only MM cells, but also MM cell-immune cell interactions and cytokine signaling. Here we examined the in vitro effects of IMiDs on cytokine signaling triggered by interaction of effector cells with MM cells and BM stroma cells. IMiDs diminished interleukin-2, interferon, and IL-6 regulator suppressor of cytokine signaling (SOCS)1 expression in immune (CD4T, CD8T, natural-killer T, natural-killer) cells from both BM and PB of MM patients. In addition, coculture of MM cells with healthy PBMCs induced SOCS1...

A New Frontier in Myeloma Therapy?

The American Society of Hematology is reporting excellent results in an investigational treatment regimen for newly diagnosed myeloma patients. This regimen which combines lenalidomide, bortezomib and dexamethasone is called "RVD" and is ...Read Full Post (Source: About.com Lymphoma)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Myelodysplastic syndromes: an update on molecular pathology

Abstract&nbsp;&nbsp;The myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid disorders characterised by impaired peripheral blood cell production due to bone marrow dysplasia affecting one or more of the major myeloid cell lines. MDS are one of five major categories of myeloid neoplasms according to the World Health Organization (WHO) classification system for haematological cancers. Given their cytological and cytogenetic heterogeneity, these diseases probably constitute a group of molecularly distinct entities with variable degrees of ineffective haematopoiesis and susceptibility to leukaemic transformation. Recent studies provide some insights into the physiopathology of MDS. In the early stages, one mechanism contributing to hypercellular marrow and peripheral blo...

Lenalidomide in Nonmetastatic Biochemically Relapsed Prostate Cancer: Results of a Phase I/II Double-Blinded, Randomized Study.

CONCLUSIONS: Lenalidomide has acceptable toxicity and is associated with long-term disease stabilization and PSA declines. Randomized studies evaluating conventional clinical disease end points in this patient population are planned. Clin Cancer Res; 16(21); 5269-76. ©2010 AACR. PMID: 20978144 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

The Treatment of Elderly Patients With Multiple Myeloma: Is More Better?

The variety of treatment options available to patients of all ages who have multiple myeloma has improved considerably in the past decade. However, elderly patients have benefited more than patients of other ages. Because elderly patients, as a group, are usually not offered autologous stem cell transplant (ASCT) as a treatment option, they have been unable to benefit from the wide application of this technique, first introduced in the late 1980s. In the past 8 years, however, thalidomide, bortezomib, and very recently lenalidomide, when combined with conventional doses of alkylators and corticosteroids, have produced marked improvements in progression-free survival (PFS) and overall survival (OS) in elderly patients. Harousseau has thoroughly reviewed the important studies documenting the...

Melphalan or No Melphalan: That Is the Question

Clinical outcomes data for all of oncology include those from trial after trial demonstrating poor outcomes in older patients with cancer. Whether these are the result of limited biologic reserve, poor performance status, or inherently worse biological disease at the time of diagnosis, such age-based disparities have continued unabated for decades. However, for the first time, older patients with multiple myeloma (MM) are starting to enjoy the kinds of remission durations and overall survival (OS) seen in younger patients. In this review by Dr. Harousseau, we see that through the use of regimens such as MPV (melphalan and prednisone plus bortezomib), MPT (melphalan and prednisone plus thalidomide), MPR (melphalan and prednisone plus lenalidomide), VMPT (bortezomib, melphalan, prednisone, a...

Multiple Myeloma in the Elderly: When to Treat, When to Go to Transplant

The objective of these improved treatment regimens should be to achieve complete response, as in younger patients. However, toxicity is a significant concern, and doses of thalidomide and of myelotoxic agents should be reduced in patients who are older than 75 years or who have poor performance status. Weekly bortezomib appears to induce severe peripheral neuropathy less frequently than the same agent administered twice weekly. Autologous stem cell transplantation is feasible in selected fit patients over 65 years of age, and its results are improved by the addition of novel agents before and after high-dose therapy. However, considering the progress in non-intensive therapy, autologous transplantation should not currently be offered to elderly patients outside of a clinical trial. (Source...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Docetaxel-based combination therapy for castration-resistant prostate cancer

Conclusions: Docetaxel-based doublet therapy remains an active investigational strategy in CRPC. Further phase III data are awaited to determine whether survival can be extended compared with docetaxel alone. (Source: Annals of Oncology)

Lenalidomide down regulates the production of interferon-gamma and the expression of inhibitory cytotoxic receptors of human Natural Killer cells.

Authors: Dauguet N, Fournié JJ, Poupot R, Poupot M Lenalidomide, a daughter molecule of Thalidomide, and IMIDs are immunomodulatory drugs that have been described as having immunomodulatory properties and anti-tumor activity. The effect of Lenalidomide towards Peripheral Blood Mononuclear Cells (PBMC) has been studied and direct effects towards T cells have been described, such as an increase of interferon-gamma (IFN-gamma) and interleukin (IL)-2 production. As a consequence, it has been also described that IL-2 subsequently activates Natural Killer (NK) cells. Nevertheless, direct effects of Lenalidomide on NK cells from healthy volunteers have never been described, if searched. Here we show that Lenalidomide can inhibit the production of IFN-gamma by NK cells from healthy donors. It...

Review: Treatment-related peripheral neuropathy in multiple myeloma

Source: Lancet Oncology Area: News In this review in Lancet Oncology on the continuing challenges of treatment-related peripheral neuropathy in multiple myeloma, the authors discuss the following issues: &nbsp; .&nbsp;Clinical presentation .&nbsp;Incidence .&nbsp;Thalidomide .&nbsp;Lenalidomide .&nbsp;Bortezomib .&nbsp;Antimyeloma drugs in development .&nbsp;Predisposing factors .&nbsp;Pathogenesis .&nbsp;Development of peripheral neuropathy: dose and treatment duration, reversibility, .&nbsp;Diagnosis .&nbsp;Prevention or intervention (Source: NeLM - News)

[Articles] Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial

Melphalan plus prednisone has been the standard treatment for elderly patients with newly diagnosed multiple myeloma for more than 30 years. It is regarded as an appropriate backbone for combination regimens containing novel agents. Findings from five randomised trials have shown that melphalan, prednisone, and thalidomide (MPT) is better than melphalan plus prednisone in terms of response rate and progression-free survival (PFS), with increased overall survival reported in three trials. Preliminary results from a randomised trial of melphalan and prednisone plus lenalidomide, with or without lenalidomide maintenance, versus standard melphalan plus prednisone have shown that the lenalidomide-containing regimen induces higher response rates than does melphalan plus prednisone alone, and tha...

Multiple myeloma in the elderly: when to treat, when to go to transplant.

The objective of these improved treatment regimens should be to achieve complete response, as in younger patients. However, toxicity is a significant concern, and doses of thalidomide and of myelotoxic agents should be reduced in patients who are older than 75 years or who have poor performance status. Weekly bortezomib appears to induce severe peripheral neuropathy less frequently than the same agent administered twice weekly. Autologous stem cell transplantation is feasible in selected fit patients over 65 years of age, and its results are improved by the addition of novel agents before and after high-dose therapy. However, considering the progress in non-intensive therapy, autologous transplantation should not currently be offered to elderly patients outside of a clinical trial. PMI...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Demonstration of additional benefit in adding lenalidomide to azacitidine in patients with higher‚?źrisk myelodysplastic syndromes

Abstract (Source: American Journal of Hematology)

Myelodysplastic syndromes in older adults.

Authors: Lindsey M, Beavers J Myelodsyplastic syndromes are a collection of disorders that affect the hematopoietic development of myeloid cells in the bone marrow. Although this disorder is curable by way of allogeneic stem cell transplantation, advanced age, limited donor availability, and multiple comorbidities often exclude patients from curative treatment. Developments using the drugs lenalidomide, decitabine, and azacitidine have offered treatment options to patients ineligible for transplantation. Nurses remain instrumental in the administration, patient monitoring, and patient education associated with these new therapies. PMID: 20880813 [PubMed - in process] (Source: Clinical Journal of Oncology Nursing)

The PD-1/PD-L1 axis modulates the natural killer cell versus multiple myeloma effect: a therapeutic target for CT-011, a novel monoclonal anti-PD-1 antibody

T-cell expression of programmed death receptor-1 (PD-1) down-regulates the immune response against malignancy by interacting with cognate ligands (eg, PD-L1) on tumor cells; however, little is known regarding PD-1 and natural killer (NK) cells. NK cells exert cytotoxicity against multiple myeloma (MM), an effect enhanced through novel therapies. We show that NK cells from MM patients express PD-1 whereas normal NK cells do not and confirm PD-L1 on primary MM cells. Engagement of PD-1 with PD-L1 should down-modulate the NK-cell versus MM effect. We demonstrate that CT-011, a novel anti&ndash;PD-1 antibody, enhances human NK-cell function against autologous, primary MM cells, seemingly through effects on NK-cell trafficking, immune complex formation with MM cells, and cytotoxicity specifical...

The antimalarial agent artesunate possesses anticancer properties that can be enhanced by combination strategies

In this study, we have explored further the activity of the clinical lead artemisinin‚?źdrug artesunate (ART), used either alone or in combination with established chemotherapy. Also, by using a cell line expressing polyploidy character, have also explored the impact of cell cycle arrest in determining overall drug activity. Results showed that ART caused dose‚?źdependent decreases in cell number, which were associated with either increased cytotoxicity or cytostasis. Cytostasis appeared to be a consequence of a simultaneous arrest at all phases of the cell cycle, a deduction that was supported by molecular profiling, which showed reductions in cell cycle transit proteins. ART appeared to maintain cells in this arrested state; however, reculturing these treated cells in drug‚?źfree medium ...

Lenalidomide¬ģ induces remission and mixed quantitative chimerism fluctuations in refractory and relapsed myeloid malignancy with del (5)

Lenalidomide, a structural analogue of thalidomide, is an immunomodulatory drug which inhibits production of pro-inflammatory cytokines and increase the secretion of anti-inflammatory cytokines from mononuclear cells (TNFőĪ and IL6), stimulate immunity by induction of cytotoxic activity of lymphocytes T and natural killer (NK), but is also an antineoplasic agent with inhibition of malignant hematopoietic cells (myeloma) and anti angiogenic agent (VEGF and bFGF) . This drug is indicated in combination with dexamethasone for treatment of multiple myeloma patients who received a prior therapy . Lenalidomide is also indicated in myelodysplastic syndromes associated with a low or intermediate risk and with a deletion 5q cytogenetic abnormality and transfusion-dependant anemia . (Source: Leukemi...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Safety and efficacy of bortezomib, melphalan and low doses dexamethasone (VM-dex) in newly diagnosed patients with multiple myeloma

In multiple myeloma patients ineligible to high-dose therapy, the addition of new drugs (i.e. bortezomib, lenalidomide, thalidomide) to melphalan and prednisone (MP) has increased notably the percentage of overall responses, particularly the complete response (CR), considered as surrogate of survival (OS) . In particular, the combination of bortezomib (V) with melphalan and prednisone (VMP) in the VISTA trial showed significant superiority respect to MP in terms of CR (30% vs 4%) and duration of response (19.9 vs 13.1 months, respectively) emerging as one of the best new therapy for elderly patients . Since V is usually administered with dexamethasone (Dex) on the same day in many combination treatments for myeloma with additive efficacy in terms of response the rationale of the use of V w...

Myocarditis During Lenalidomide Therapy (November).

CONCLUSIONS: Our findings suggest that lenalidomide may be a cause of drug-induced myocarditis. When patients treated with lenalidomide present with signs and symptoms of heart failure in the absence of other obvious causes, lenalidomide hypersensitivity should be considered in the differential diagnosis and a myocardial biopsy should be considered when other common causes of heart failure have been excluded. A reasonable management approach is drug discontinuation and early institution of corticosteroid therapy. An objective causality assessment, using the Naranjo probability scale, revealed that the adverse drug event was probable. PMID: 20876827 [PubMed - as supplied by publisher] (Source: The Annals of Pharmacotherapy)

Treatment of relapsed and refractory multiple myeloma in the era of novel agents

Abstract: The introduction of the Immunomodulatory drugs (IMiDs) and proteasome inhibitors, used either as a single-agent or combined with classic anti-myeloma therapies, has improved the outcome for patients with relapsed myeloma. However, there is currently no generally accepted standard treatment for relapsed/refractory myeloma patients, partly because of the absence of trials comparing the efficacy of the novel agents in relapsed/refractory myeloma. Choice of a new treatment regimen depends on both patient and disease-specific characteristics. A lenalidomide-based regimen is the first choice in patients with neuropathy, while bortezomib has the highest efficacy in patients with renal insufficiency and is not associated with increased risk of thromboembolism. A second autologous stem ce...

Forty-five new members join DF/HCC

Forty-five individuals have recently joined DF/HCC. See below to learn more about these scientists and their research interests. &nbsp; &nbsp; Reza Abdi, MD (BWH) Cancer Immunology Research focus: The lab focuses on identifying antigen dependent and independent factors which may result in development and progression of chronic renal allograft dysfunction. They research the roles of chemokines in the pathogenesis of allograft rejection, ischemia renal injuries and diabetes, and are planning to carry out novel approaches to study the role of chemokines in allograftrejection. &nbsp; Andrew Bellizzi, MD (BWH) Gastrointestinal Malignancies Research focus: The lab conducts clinical and translational research in gastrointestinal, pancreatobiliary, and head and neck path...

Lenalidomide in combination with dexamethasone: effective regimen in patients with relapsed or refractory multiple myeloma complicated by renal impairment

In conclusion, lenalidomide plus dexamethasone is an effective regimen for relapsed or refractory patients with MM complicated by RI with manageable toxicity. Content Type Journal ArticleDOI 10.1007/s00277-010-1080-4Authors Ulrike Klein, Department of Internal Medicine V, Hematology and Oncology, University of Heidelberg, INF 410, 69120 Heidelberg, GermanyKai Neben, Department of Internal Medicine V, Hematology and Oncology, University of Heidelberg, INF 410, 69120 Heidelberg, GermanyThomas Hielscher, Department of Biostatistics, German Cancer Research Centre, INF 280, 69120 Heidelberg, GermanyChristiane Hei√?, Department of Biostatistics, German Cancer Research Centre, INF 280, 69120 Heidelberg, GermanyAnthony D. Ho, Department of Internal Medicine V, Hematology and Oncology, Univ...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Lenalidomide enhances antibody-dependent cellular cytotoxicity of solid tumor cells in vitro: influence of host immune and tumor markers

Abstract&nbsp;&nbsp;We evaluated the effect of combining lenalidomide with therapeutic antibodies on antibody-dependant cell-mediated cytotoxicity (ADCC) of solid tumor cells, and the requirement for expression of natural killer (NK) cell-activating receptors and their solid tumor surface ligands. Twenty-three human tumor cell lines (colon, breast, lung, head and neck, ovary, and bone sarcoma) were analyzed. NK effector cells were isolated from healthy donors, pre-treated with and without lenalidomide, and incubated with antibody-coated tumor cells to determine ADCC. In blocking experiments, NK cells were pre-incubated with anti-DNAM-1 or anti-NKG2D antibodies, and target colorectal cells were pre-incubated with anti-CD155 (PVR), anti-MIC-A/B, or anti-ULBP 3 antibodies. Differences b...

Durable hematologic complete responses can be achieved with lenalidomide in AL amyloidosis

(No abstract is available for this citation) (Source: Blood)

A phase I study of lenalidomide in combination with fludarabine and rituximab in previously untreated CLL/SLL

A phase I study of lenalidomide in combination with fludarabine and rituximab in previously untreated CLL&#47;SLL Leukemia advance online publication, September 16, 2010. doi:10.1038/leu.2010.199 Authors: J R Brown, J Abramson, E Hochberg, E Mikler, V Dalton, L Werner, H Reynolds, C Thompson, S M McDonough, Y Kuang, J Ritz, D Neuberg & A S Freedman (Source: Leukemia)

Natco Pharma open to settle cancer drug patent case with US co

Natco Pharma Ltd on Friday did not rule out a settlement over the patent issue with Celgene Corp, which has said it would file a complaint against the former for alleged infringement of its cancer drug Revlimid. (Source: The Economic Times Healthcare and Biotech News)

MDS Remission Often Isn't (CME/CE)

(MedPage Today) -- Patients who had a "complete" remission of myelodysplastic syndrome (MDS) after treatment with lenalidomide (Revlimid) still had circulating drug-resistant malignant stem cells -- and the disease resumed its progression in most patients despite continued treatment, a small study found. (Source: MedPage Today Hematology/Oncology)

Pomalidomide (CC4047) plus low dose dexamethasone (Pom/dex) is active and well tolerated in lenalidomide refractory multiple myeloma (MM)

Pomalidomide (CC4047) plus low dose dexamethasone (Pom&#47;dex) is active and well tolerated in lenalidomide refractory multiple myeloma (MM) Leukemia advance online publication, September 9, 2010. doi:10.1038/leu.2010.190 Authors: M Q Lacy, S R Hayman, M A Gertz, K D Short, A Dispenzieri, S Kumar, P R Greipp, J A Lust, S J Russell, D Dingli, S Zeldenrust, R Fonseca, P L Bergsagel, V Roy, J R Mikhael, A K Stewart, K Laumann, J B Allred, S J Mandrekar, S V Rajkumar & F Buadi (Source: Leukemia)

Celgene Officially Notified Of ANDA Filing For REVLIMID(R)

Celgene Corporation (NASDAQ:√?ÔŅĹCELG) announced it has received a Paragraph IV Certification Letter advising that Natco Pharma Limited of Hyderabad, India, submitted an Abbreviated New Drug Application (ANDA) to the U.S. Food and Drug Administration (FDA). The application requests authorization to manufacture and market generic versions of REVLIMID¬ģ (lenalidomide) 5, 10, 15 and 25 mg capsules in the United States... (Source: Health News from Medical News Today)

Celgene Officially Notified Of ANDA Filing For REVLIMID

Celgene Corporation today announced it has received a Paragraph IV Certification Letter advising that Natco Pharma Limited of Hyderabad, India, submitted an Abbreviated New Drug Application (ANDA) to the U.S. Food and Drug Administration (FDA). (Source: Pharmaceutical Online News)

Revlimid (Lenalidomide) - updated on RxList

Revlimid (Lenalidomide) drug description - FDA approved labeling for prescription drugs and medications at RxList (Source: RxList - New and Updated Drug Monographs)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Lenalidomide for bortezomib-resistant multiple myeloma

Authors: Chiara Briani, Tamara Berno, Marta Campagnolo & Renato Zambello We read with great interest the paper by Ludwig and Zojer reporting a patient with bortezomib-resistant multiple myeloma who achieved renal recovery after lenalidomide therapy (Renal recovery with lenalidomide in a patient with bortezomib-resistant multiple myeloma. Nat. Rev. Clin. Oncol.7, 289 (Source: Nature Clinical Practice Oncology)

Lenalidomide efficacy in bortezomib-resistant myeloma

Authors: Alessandro Gozzetti, Rosaria Crupi, Marzia Defina & Monica Bocchia We read with great interest the Case Study by Ludwig and Zojer in which they describe a case of a 51-year-old man with IgG &#955; stage III B multiple myeloma who presented with renal impairment associated with urinary secretion of free &#955; chains (Renal (Source: Nature Clinical Practice Oncology)

Author reply: Lenalidomide for bortezomib-resistant multiple myeloma

Authors: Heinz Ludwig & Niklas Zojer We thank Briani et al. and Gozzetti et al. for their additional comments to the topics discussed in our Case Study. Briani and colleagues report on their experience with lenalidomide treatment in patients with relapsed or refractory disease (Source: Nature Clinical Practice Oncology)

Localized graft-versus-host disease of the skin provoked by radiotherapy

In multiple myeloma allogeneic stem cell transplantation (allo-SCT) is associated with the highest rate of molecular remissions and a lower risk of recurrence compared with other treatment options including autologous SCT . This is due to the graft-versus-myeloma effect, which was proven by the achievement of sustained complete remissions by donor lymphocyte infusions (DLIs) without any other therapy in patients with relapse after both myeloablative and non-myeloablative allo-SCT . However, because of high treatment-related mortality especially after myeloablative conditioning and the introduction of novel agents such as bortezomib and the immunomodulatory drugs thalidomide and lenalidomide, the value of this approach remains to be determined in clinical trials. (Source: Leukemia Research)

Treatment of patients with relapsed/refractory multiple myeloma with lenalidomide and dexamethasone with or without bortezomib: prospective evaluation of the impact of cytogenetic abnormalities and of previous therapies

Treatment of patients with relapsed&#47;refractory multiple myeloma with lenalidomide and dexamethasone with or without bortezomib: prospective evaluation of the impact of cytogenetic abnormalities and of previous therapies Leukemia advance online publication, August 26, 2010. doi:10.1038/leu.2010.175 Authors: M A Dimopoulos, E Kastritis, D Christoulas, M Migkou, M Gavriatopoulou, M Gkotzamanidou, M Iakovaki, C Matsouka, D Mparmparoussi, M Roussou, E Efstathiou & E Terpos (Source: Leukemia)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Solitary Extramedullary Plasmacytoma of the Bladder: A Case Report and Literature

Plasmacytoma is a rare B-lymphocyte neoplastic disorder that usually presents as the generalized disease multiple myeloma. Less than 5% of the cases present as a solitary mass of monoclonal plasma cells in the bone or soft tissue. Although solitary extramedullary plasmacytoma (SEP) may arise in any organ, it rarely involves the urinary bladder. A 67-year-old male without a history of multiple myeloma presented with urinary frequency and nocturia; he was later diagnosed with SEP of the bladder. The patient was initially treated with a course of radiation therapy without symptomatic improvement; therefore a chemotherapy regimen consisting of lenalidomide and dexamethasone was subsequently given for six cycles. SEP usually carries a better prognosis and higher cure rate than solitary plasmacy...

Solitary Extramedullary and Bone Plasmacytomas versus Multiple Myeloma with Extramedullary Manifestation

Extramedullary disease in plasma cell disorders can occur as a solitary plasmacytoma or can involve multiple sites with vastly different clinical outcomes. The article by Khaliq et al reports an unusual case of solitary extramedullary plasmacytoma (SEP) of the bladder in which the patient had a favorable outcome with lenalidomide/dexamethasone after failing first-line treatment with radiotherapy. In this context it is interesting to compare clinical outcomes of this entity to two other clinical variants of myeloma: solitary plasmacytoma of bone (SPB), and multiple myeloma with extramedullary plasmacytomas (MM/EP). (Source: Cancer Network)

Lenalidomide approved in Japan for treatment of deletion 5q myelodysplastic syndromes

Source: BioSpace Area: News According to BioSpace, lenalidomide (Revlimid?) has been granted full marketing authorisation by Japan's Ministry of Health, Labour and Welfare (MHLW) for the treatment of patients with myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenic abnormality. &nbsp; Lenalidomide is currently approved in the UK for use in combination with dexamethasone for the treatment of multiple myeloma patients who have received at least one prior therapy. (Source: NeLM - News)

REVLIMID(R) Approved for Treatment of Deletion 5q Myelodysplastic Syndromes in Japan

BOUDRY, Switzerland--(Healthcare Sales & Marketing Network)--Celgene International S&agrave;rl (NASDAQ: CELG ) announced that REVLIMID (lenalidomide) has been granted full marketing authorization by Japan¬?s Ministry of Health, Labour and Welfare (MHLW) for... Biopharmaceuticals, Oncology, RegulatoryCelgene, REVLIMID, lenalidomide, myelodysplastic syndrome (Source: HSMN NewsFeed)

Efficacy of the association of lenalidomide to erythropoiesis-stimulating agents in del (5q) MDS patients refractory to single-agent lenalidomide

Authors: S Park, D Vassilieff, V Bardet, F Vigui&#233; & F Dreyfus (Source: Leukemia)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Lenalidomide-Induced Acute Interstitial Nephritis.

Authors: Lipson EJ, Huff CA, Holanda DG, McDevitt MA, Fine DM PMID: 20709889 [PubMed - as supplied by publisher] (Source: The Oncologist)

Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma

This study is registered at http://clinicaltrials.gov as NCT00378105. (Source: Blood)

Combined proteasome and histone deacetylase inhibition: A promising synergy for patients with relapsed/refractory multiple myeloma

Abstract: Multiple myeloma (MM) is an incurable disease characterized by the accumulation of malignant plasma cells in the bone marrow. Recently, an improved understanding of the biology of the disease has led to the development of targeted agents such as the proteasome inhibitor bortezomib and the immunomodulatory agents thalidomide and lenalidomide; however, MM remains incurable. The combination of bortezomib and an HDAC inhibitor synergistically induces MM cell apoptosis and may be of value in the treatment of patients with relapsed/refractory MM. This review examines the potential of combined proteasome and HDAC inhibition in the treatment of relapsed/refractory MM. (Source: Leukemia Research)

Lenalidomide: Thrombocytopenia and neutropenia in elderly patients: 2 case reports

(Source: Reactions)

Management of patients with chronic lymphocytic leukemia treated with lenalidomide.

Authors: Miller KC, Musial L, Whitworth A, Chanan-Khan A Lenalidomide is an immunomodulatory drug that has shown preliminary activity in the treatment of chronic lymphocytic leukemia (CLL). Much is known about the safety profile of lenalidomide from experience in other hematologic malignancies, such as myelodysplastic syndromes and multiple myeloma. In addition to the known adverse effects associated with lenalidomide (e.g., myelosuppression, rash, fatigue), some unique effects (e.g., tumor flare reactions, tumor lysis syndrome) have arisen during clinical studies of CLL. Typical signs of tumor flare reactions include early onset of painful enlargement of the lymph nodes or spleen, with or without low-grade fever, rash, and bone pain. Management may require nonsteroidal anti-inflammato...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Thalidomide and lenalidomide in primary myelofibrosis.

We describe the experience with these drugs in a cohort of 14 patients for thalidomide and seven for lenalidomide (in six patients lenalidomide was given after thalidomide and one patient received lenalidomide upfront). Thalidomide gave clinical improvement in 6/14 patients, but its use was limited mainly due to toxicity, especially the development of neuropathy. The drug could be given for a median period of 15.5 months in responding patients. Lenalidomide was effective in 4/7 of the patients, in some patients with no response on thalidomide. Due to the more favourable toxicity profile, the median duration of therapy was 19 months, with 3/4 patients on therapy longer than 19 months. These data are discussed in view of the clinical studies published. We conclude that lenalidomide is prefer...

LETTER TO THE EDITOR: Activity and safety of lenalidomide and dexamethasone in patients with multiple myeloma requiring dialysis: a Spanish multicenter retrospective study

(Source: European Journal of Haematology)

Solitary extramedullary plasmacytoma of the bladder: a case report and literature.

Authors: Khaliq W, Uzoaru I, Konchanin RP, Sapiente RA, Egner JR Plasmacytoma is a rare B-lymphocyte neoplastic disorder that usually presents as the generalized disease multiple myeloma. Less than 5% of the cases present as a solitary mass of monoclonal plasma cells in the bone or soft tissue. Although solitary extramedullary plasmacytoma (SEP) may arise in any organ, it rarely involves the urinary bladder. A 67-year-old male without a history of multiple myeloma presented with urinary frequency and nocturia; he was later diagnosed with SEP of the bladder. The patient was initially treated with a course of radiation therapy without symptomatic improvement; therefore a chemotherapy regimen consisting of lenalidomide and dexamethasone was subsequently given for six cycles. SEP usually c...

Revlimid capsules (Lenalidomide) - Revised SPC

Source: eMC (electronic Medicines Compendium) Area: Other Library Updates > SPC Changes ?Revised SPC changes include: Section 4.4: Cardiovascular Disorders and Mycardial Infarction have been added. Section 4.8: Myocardial Infarction added as a common side effect to Cardiovascular Disorders. Interstitial pneumonitis (frequency unknown) added to Respiratory, thoracic and mediastinal disorders. Pancreatitis (frequency unknown) added to Gastrointestinal disorders. (Source: NeLM - SPC Changes)

Lenalidomide: Hypersensitivity pneumonitis in an elderly patient: case report

(Source: Reactions)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Lenalidomide: Hypersensitivity pneumonitis: case report

(Source: Reactions)

Onyx Pharmaceuticals Initiates A Phase 3 Carfilzomib Combination Trial In Relapsed Multiple Myeloma

Onyx Pharmaceuticals, Inc. (Nasdaq: ONXX) announced that the company has begun enrollment in the ASPIRE trial, a Phase 3 international clinical trial evaluating carfilzomib in combination with lenalidomide (Revlimid¬ģ) and low dose dexamethasone in patients with relapsed multiple myeloma. The company has an agreement with the U.S. Food and Drug Administration (FDA) on a Special Protocol Assessment (SPA) and received Scientific Advice from the European Medicines Agency (EMA) on the design and planned analysis of the ASPIRE trial... (Source: Health News from Medical News Today)

Chemomobilization with Etoposide is Highly Effective in Patients with Multiple Myeloma and Overcomes the Effects of Age and Prior Therapy

The optimal mobilization strategy prior to autologous stem cell transplantation for patients with multiple myeloma remains unclear. Mobilization with cytokines alone appears to yield suboptimal results in older patients as well as patients who have received prior lenalidomide. To avoid the marked cytopenias and risks of hemorrhagic cystitis associated with the administration of cyclophosphamide, we investigated the efficacy and safety of chemomobilization with an intermediate dose etoposide (VP-16; 375 mg/m2 on days +1 and +2) and granulocyte-colony stimulating factor (G-CSF) (5 őľg/kg twice daily from day +3 through the final day of collection). We reviewed our institutional experience with 152 myeloma patients mobilized with this regimen. The addition of VP-16 to G-CSF resulted in succes...

Efficacy of single-agent lenalidomide in patients with JAK2 (V617F) mutated refractory anemia with ring sideroblasts and thrombocytosis

We report the results of lenalidomide treatment in these patients and show that lenalidomide has clinical activity in this rare disorder. Both patients became transfusion independent, and 1 of the patients attained indeed a complete molecular remission. (Source: Blood)

Thyroid dysfunction is a relatively rare occurrence with thalidomide or lenalidomide

(Source: Reactions)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Lenalidomide: Interstitial lung disease in an elderly patient: case report

(Source: Reactions)

Development of target-specific treatments in multiple myeloma

In the last decade, the novel agents lenalidomide, bortezomib, and thalidomide have dramatically improved outcomes for patients with multiple myeloma (MM). A number of new therapies with precise targets involved in MM cell growth and replication are now in development and have the potential for further improvements. Second-generation proteasome inhibitors and thalidomide derivatives may offer increased efficacy and safety. Investigational therapies with rationally selected targets in MM include inhibitors of histone deacetylase, heat shock protein 90, mammalian target of rapamycin, BCL2, Akt, mitogen-activated protein kinase, and telomerase. In addition, monoclonal antibodies directed against several targets have been developed and many are showing promise in initial clinical trials in MM....

[Assessing lenalidomide for treating multiple myeloma, myelofibrosis and myelodysplastic syndrome.]

CONCLUSION: LDM is well-tolerated and produces sustained clinical benefits, especially in MM and MF. More studies are needed for in-depth examination of treatment duration, new indications and the use of treatments combined with other drugs. PMID: 20615740 [PubMed - as supplied by publisher] (Source: Farmacia Hospitalaria)

Erratum to: Lenalidomide plus dexamethasone treatment in Japanese patients with relapsed/refractory multiple myeloma.

Authors: Iida S, Chou T, Okamoto S, Nagai H, Hatake K, Murakami H, Takagi T, Shimizu K, Lau H, Takeshita K, Takatoku M, Hotta T PMID: 20593310 [PubMed - as supplied by publisher] (Source: International Journal of Hematology)

Activity and safety of lenalidomide and dexamethasone in multiple myeloma patients requiring dialysis: a Spanish multicenter retrospective study.

(Source: European Journal of Haematology)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Changes in RPS14 expression levels during lenalidomide treatment in Low‚?ź and Intermediate‚?ź1‚?źrisk myelodysplastic syndromes with chromosome 5q deletion

(Source: European Journal of Haematology)

Early response assessment in patients with multiple myeloma during anti-angiogenic therapy using arterial spin labelling: first clinical results

Conclusion&nbsp;&nbsp;ASL tumour perfusion measurements are a valuable surrogate parameter for early assessment of response to novel anti-angiogenic therapy. Content Type Journal ArticleCategory OncologyDOI 10.1007/s00330-010-1870-zAuthors Michael Fenchel, Eberhard-Karls University Department of Diagnostic and Interventional Radiology Hoppe-Seyler-Str. 3 72076 Tuebingen GermanyMarina Konaktchieva, Eberhard-Karls University Department of Internal Medicine, Gastroenterology Tuebingen GermanyKatja Weisel, Eberhard-Karls University Department of Internal Medicine, Hematology Tuebingen GermanySabina Kraus, Eberhard-Karls University Department of Internal Medicine, Hematology Tuebingen GermanyHarald Brodoefel, Eberhard-Karls University Department of Diagnostic and Interventional Radi...

Phase III studies demonstrate significantly superior progression free survival with continuous revlimid therapy in diagnosed multiple myeloma

Data presented at ASCO and EHA showed unprecedented clinical benefit of continuous revlimid after autologous stem cell transplant (Source: Pharmacy Europe)

Improved survival of multiple myeloma patients with late relapse after high-dose treatment and stem cell support, a population-based study of 348 patients in Denmark in 1994&#x2013;2004*

Conclusion: Improved survival was only observed among patients with late relapse after HDT and this may be because of increased use of salvage HDT, improved supportive care and introduction of new drugs. (Source: European Journal of Haematology)

Targeted treatment and new agents in follicular lymphoma.

Authors: Cheson BD Follicular lymphomas are indolent diseases, which, while highly responsive to chemotherapy, remain incurable. Various combinations of standard chemotherapy drugs have not improved the outcome. The availability of effective and well-tolerated monoclonal antibodies (MoAbs), such as rituximab, provided the first evidence that new agents could prolong the survival of these patients. An increasing number of effective drugs are now being evaluated either as single agents or in combinations. These include chemotherapy drugs, bendamustine and bortezomib, MoAbs, other agents that inhibit various cellular pathways including spleen tyrosine kinase, mammalian target of rapamycin, PI3-kinase and apoptosis, and drugs that target the tumor microenvironment, such as the immunomodula...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Interim report of a phase 2 clinical trial of lenalidomide for T-cell non-Hodgkin lymphoma

Novel therapies are needed to improve outcomes in T-cell lymphomas. The authors report the interim results of a prospective multicenter trial evaluating lenalidomide in T-cell lymphomas.Patients with recurrent and refractory T-cell lymphomas other than mycosis fungoides and untreated patients ineligible for combination chemotherapy were prescribed oral lenalidomide (25 mg daily) on Days 1 to 21 of each 28-day cycle until disease progression, death, or unacceptable toxicity. The primary endpoint was overall response rate. Secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. The 2-stage design allows for up to 40 patients.At the time of this interim analysis, 24 patients were enrolled in this study, and 23 were evaluable for response. The median age wa...

Lenalidomide plus dexamethasone treatment in Japanese patients with relapsed/refractory multiple myeloma.

In conclusion, 25 mg of lenalidomide was given safely as a single agent or in combination with dexamethasone in Japanese patients. The good efficacy of the combination therapy was also demonstrated in this study. PMID: 20559759 [PubMed - as supplied by publisher] (Source: International Journal of Hematology)

Study Identifies Promising Treatment for Aggressive Lymphoma

New research illustrates that some patients with transformed lymphoma showed "remarkable" response to lenalidomide, an oral drug with few side effects. (Source: News from Mayo Clinic)

Updated results for Revlimid

Updated results of phase III study evaluating continuous Revlimid therapy in newly diagnosed multiple myeloma (Source: Pharmacy Europe)

Plasma cell leukaemia and other aggressive plasma cell malignancies

Extramedullary plasma cell cancers, such as plasma cell leukaemia (PCL) and multiple extramedullary plasmacytomas (MEP) are very aggressive malignancies. These can be primary (de-novo) or secondary due to progressive prior multiple myeloma (MM). Recent reports suggest an increase in incidence of these disorders. Compared to MM, organ invasion is common in PCL, while soft tissue tumors involving the head, neck or paraspinal area are common sites for MEP. Markers of poor prognosis are frequently observed in these extramedullary forms of plasma cell cancers, and survival is significantly inferior compared to patients with MM. Conventional chemotherapeutic and radiotherapy approaches have been employed with variable results. Even high dose chemotherapy with autologous stem cell rescue has not ...

The addition of cyclophosphamide to lenalidomide and dexamethasone in multiply relapsed/refractory myeloma patients; a phase I/II study

We report the results of a Phase I/II dose escalation study to determine the maximum tolerated dose (MTD) of cyclophosphamide when combined with lenalidomide and dexamethasone in relapsed/refractory myeloma. Thirty-one patients were enrolled in cohorts of 3, at five dose levels of cyclophosphamide to a maximum of 700 mg on days 1 and 8 of a 28-d cycle. Patients received lenalidomide 25 mg days 1[ndash]21 and dexamethasone 20 mg orally days 1[ndash]4 and 8[ndash]11. The MTD was 600 mg cyclophosphamide, days 1 and 8. Grade 3/4 haematological complications occurred in 26% of patients, grade 3/4 infection in 3% (both at 700 mg cyclophosphamide), with thromboembolic complications in 6% of patients. Overall complete response (CR) rate was 29%, very good partial response rate 7% and partial respo...

Management of relapsed or refractory multiple myeloma in French hospitals and estimation of associated direct costs: a multi-centre retrospective cohort study

What is known and background: For relapsed or refractory multiple myeloma (RRMM), a series of novel agents (thalidomide, bortezomib and lenalidomide) has emerged during the latest decade, but their use in routine clinical practice is not well documented as well as the cost of RRMM.Objective: Our aim is to review the therapeutic management of such patients in France and to estimate the associated costs.Methods: A retrospective cohort study, based on chart reviews, was conducted in French Haematology Departments over the period 2004[ndash]2007 and the associated direct costs estimated.Results: One hundred and two patients with a relapse after first-line therapy were selected from five centres. The average follow-up from diagnosis or the date of first relapse to death or to the latest news wa...

Conference report: Continuous lenalidomide linked to improved progression free survival in patients with multiple myeloma following autologous stem cell transplant

Source: BioSpace Area: News According to data from the phase III, Intergroupe Francophone du Myelome (IFM 2005 02) study presented at ASCO, continuous lenalidomide treatment of patients with multiple myeloma following a first-line autologous stem cell transplant (ASCT) was associated with superior 3-year progression-free survival (PFS). &nbsp; The study involved patients who achieved at least stable disease following ASCT (within previous 6months) who were randomised to receive a two-month consolidation regimen of lenalidomide monotherapy 25mg 21/28 days (no steroids included), followed by continuous daily treatment with either placebo (n=307) or lenalidomide 10-15 mg (n=307) until relapse. At the first planned interim analysis, the independent Data and Safety Monitoring Committee rec...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Targeted treatment and new agents in peripheral T-cell lymphoma.

Authors: Zain JM, O'Connor O Mature T-cell and NK-cell lymphomas are increasingly being recognized as unique biological entities distinguishable from other forms of lymphomas. Treatment paradigms developed for B-cell lymphomas are considered inadequate for application to these diseases, as indicated by the poor outcome of these patients with the overall 5-year survival remaining below 30% for most histologies. There is a tremendous need for newer treatment options both in the upfront and relapsed setting for T-cell lymphomas. In recent years, there has been a plethora of new targeted agents that have shown promising activity in T-cell lymphomas. The most notable is the novel antifolate pralatrexate that has been approved for the treatment of relapsed and refractory T-cell lymphoma. Oth...

Maintenance Treatment With Oral Lenalidomide After Stem Cell Transplant Reduces Risk Of Disease Progression For Multiple Myeloma Patients

Updated data from a National Cancer Institute-sponsored clinical trial conducted by the Cancer and Leukemia Group B (CALGB) are being presented at the 46th annual meeting of the American Society of Clinical Oncology in Chicago. The study evaluated the benefits of maintenance treatment with lenalidomide (Revlimid¬ģ) administered orally following an autologous stem cell transplant for patients with newly diagnosed multiple myeloma, compared to placebo. Maintenance therapy is an ongoing treatment given after patients achieve remission with initial therapy to try to prolong remission... (Source: Health News from Medical News Today)

Gene expression profiling for diagnosis and therapy in acute leukaemia and other haematologic malignancies

Abstract: A decade ago, gene expression profiling (GEP) was successfully introduced in haematological research. Considering the heterogeneity of haematological malignancies, the growing arsenal of compounds, allowing targeted therapy, e.g. in myelodysplastic syndromes (MDS) or chronic myeloid leukaemia (CML), and the more differentiated indication to allogeneic stem cell transplantation, routine diagnostic procedures would highly benefit from an introduction of this novel methodology: by now, the majority of genetically defined leukaemia subtypes has been accurately reproduced on the basis of distinct gene expression patterns by various independent research groups. Moreover, classification of histomorphologically overlapping lymphoma subentities (e.g. Burkitt lymphoma and diffuse large B-c...

Clarithromycin (Biaxin)-lenalidomide-low-dose dexamethasone (BiRd) versus lenalidomide-low-dose dexamethasone (Rd) for newly diagnosed myeloma

The objective of this case-matched study was to compare the efficacy and toxicity of the addition of clarithromycin (Biaxin) to lenalidomide/low-dose dexamethasone (BiRd) vs. lenalidomide/low-dose dexamethasone (Rd) for newly diagnosed myeloma. Data from 72 patients treated at the New York Presbyterian Hospital-Cornell Medical Center were retrospectively compared with an equal number of matched pair mates selected among patients seen at the Mayo Clinic who received Rd. Case matching was blinded and was performed according to age, gender, and transplant status. On intention-to-treat analysis, complete response (45.8% vs. 13.9%, P < 0.001) and very-good-partial-response or better (73.6% vs. 33.3%, P < 0.001) were significantly higher with BiRd. Time-to-progression (median 48.3 vs. 27.5 month...

Immunomodulatory Agents with Antivascular Activity in the Treatment of Non-Small Cell Lung Cancer: Focus on TLR9 Agonists, IMiDs and NGR-TNF

Standard treatments for nonsmall cell lung cancer (NSCLC), such as surgery, chemotherapy, and radiotherapy, often lead to disappointing results. Unfortunately, also the various immunotherapeutic approaches so far tested have not produced satisfactory results to be widely applied in the clinical practice. However, the recent development of new immunomodulatory agents may open promising therapeutic options. This paper focuses on PF3512676, lenalidomide, and NGR-TNF, that is, drugs belonging to three different classes of immunomodulatory agents, that are also capable to affect tumor blood vessels with different mechanisms, and discusses the potential role of such agents in NSCLC treatment strategy. (Source: Journal of Oncology)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

An update on the treatment of myelodysplastic syndromes.

Authors: Kurtin SE, Demakos EP Myelodysplastic syndromes (MDS) are a group of heterogeneous clonal disorders of myeloid hematopoietic stem cells affecting about 300,000 people worldwide. Ineffective hematopoiesis and clonal proliferation result in significant cytopenias in affected individuals. Patients are categorized into risk groups (i.e., low, intermediate [1 and 2], and high) based on severity of cytopenias, cytogenetic abnormalities, and the presence of bone marrow blasts. The only potentially curative treatment for MDS is hematopoietic stem cell transplantation, which often is not an option because of advanced age at diagnosis (median age = 76 years). Several alternative treatments to hematopoietic stem cell transplantation show great promise. For low- and intermediate-1-risk MD...

Evidence for Cytogenetic and Fluorescence In Situ Hybridization Risk Stratification of Newly Diagnosed Multiple Myeloma in the Era of Novel Therapie

This study validates the high-risk features defined by FISH and CG in the Mayo risk-stratification model for patients with MM predominantly treated with novel therapies based on immunomodulatory agents. (Source: Mayo Clinic Proceedings)

Evidence for Cytogenetic and Fluorescence In Situ Hybridization Risk Stratification of Newly Diagnosed Multiple Myeloma in the Era of Novel Therapies

This study validates the high-risk features defined by FISH and CG in the Mayo risk-stratification model for patients with MM predominantly treated with novel therapies based on immunomodulatory agents. (Source: Mayo Clinic Proceedings)

Lenalidomide induced good clinical response in a patient with multiple relapsed and refractory Hodgkin's lymphoma

Conclusion: Daily, long-term lenalidomide treatment provided clinical benefit and was well tolerated in a patient with relapsed, advanced classic Hodgkin's lymphoma. (Source: BioMed Central)

Superior results of Total Therapy 3 (2003-33) in gene expression profiling-defined low-risk multiple myeloma confirmed in subsequent trial 2006-66 with VRD maintenance

We report here on the results of successor trial 2006-66 with 177 patients, using bortezomib, lenalidomide, and dexamethasone maintenance for 3 years versus bortezomib, thalidomide, and dexamethasone in year 1 and thalidomide/dexamethasone in years 2 and 3 in the 2003-33 protocol. Overall survival (OS) and event-free survival (EFS) plots were super-imposable for the 2 trials, as were onset of complete response and complete response duration (CRD), regardless of GEP risk. GEP-defined high-risk designation, pertinent to 17% of patients, imparted inferior OS, EFS, and CRD in both protocols and, on multivariate analysis, was the sole adverse feature affecting OS, EFS, and CRD. Mathematical modeling of CRD in low-risk myeloma predicted a 55% cure fraction (P &lt; .001). Despite more rapid onset...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

A Case of Lenalidomide-Induced Hypersensitivity Pneumonitis.

Conclusions: Given the frequently reported pulmonary infectious complications in patients treated with lenalidomide and a possibly underreported rate of interstitial pneumonitis, we advocate a more aggressive pulmonary workup for patients with pulmonary symptoms. PMID: 20502059 [PubMed - as supplied by publisher] (Source: Onkologie)

Lenalidomide-induced hypersensitivity pneumonitis.

Authors: Kortuem M, Einsele H PMID: 20502054 [PubMed - in process] (Source: Onkologie)

Study Identifies Promising Treatment For Aggressive Lymphoma

New research illustrates that some patients with transformed lymphoma showed "remarkable" response to lenalidomide, an oral drug with few side effects. VIDEO ALERT: Additional audio and video resources, including excerpts from an interview with Dr. Craig Reeder, are available on the Mayo Clinic News Blog. The international study, involving 24 medical centers in the United States and Europe, will be presented at the American Society of Clinical Oncology annual meeting June 4-8, 2010, in Chicago... (Source: Health News from Medical News Today)

Promising treatment for aggressive lymphoma identified in new study

New research illustrates that some patients with transformed lymphoma showed "remarkable" response to lenalidomide, an oral drug with few side effects. (Source: ScienceDaily Headlines)

Bortezomib, dexamethasone, cyclophosphamide and lenalidomide combination for newly diagnosed multiple myeloma: phase 1 results from the multicenter EVOLUTION study

Authors: S K Kumar, I Flinn, S J Noga, P Hari, R Rifkin, N Callander, M Bhandari, J L Wolf, C Gasparetto, A Krishnan, D Grosman, J Glass, E A Sahovic, H Shi, I J Webb, P G Richardson & S V Rajkumar (Source: Leukemia)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Study Identifies Promising Treatment for Aggressive Lymphoma

New research illustrates that some patients with transformed lymphoma showed "remarkable" response to lenalidomide, an oral drug with few side effects. (Source: News from Mayo Clinic)

Maintenance with lenalidomide extended PFS after ASCT for multiple myeloma

(Source: HemOncToday.com)

Study identifies promising treatment for aggressive lymphoma

(Mayo Clinic) New research illustrates that some patients with transformed lymphoma showed "remarkable" response to lenalidomide, an oral drug with few side effects. (Source: EurekAlert! - Medicine and Health)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

The efficacy and safety of lenalidomide plus dexamethasone in relapsed and/or refractory multiple myeloma patients with impaired renal function

In patients with multiple myeloma, renal impairment (RI) at the time of diagnosis is associated with poor survival. To the authors' knowledge, the current retrospective analysis presented is the first to assess the impact of various degrees of renal dysfunction on safety and efficacy outcomes in a large cohort of patients with relapsed and/or refractory multiple myeloma who received treatment with lenalidomide plus dexamethasone.Three hundred fifty-three patients from 2 large phase 3 trials were randomized to receive lenalidomide (25 mg) plus dexamethasone (40 mg). For the purpose of this analysis, RI was defined according to the calculated creatinine clearance (CLCr) level as follows: mild or no RI (CLCr [ge] 60 mL/minute), moderate RI (CLCr from [ge] 30 mL/minute to (Source: Cancer)

Efficacy to lenalidomide treatment and complete cytogenetic remission in a case of myelodysplastic syndrome with del(5q) and del(9q)

Lenalidomide is a novel thalidomide analogue with enhanced immunomodulatory and antiangiogenic action. Evidences have been accumulating suggesting that lenalidomide has a dramatic effect on 5q syndrome leading to transfusion independence, complete pathological and cytogenetic response in over two-thirds of cases . Vitro studies have suggested a selective inhibitory effect of lenalidomide on the clone with 5q deletion . Moreover, some complete cytogenetic responses were seen in patients with 5q deletion and additional cytogenetic findings, suggesting that clones with 5q deletion and additional (putatively secondary) abnormalities may also be specifically targeted by lenalidomide . Preliminary results suggest that lenalidomide also has meaningful activity in non-deletion 5q MDS, but transfus...

Mantle cell lymphoma arising in a multiple myeloma patient responding to lenalidomide

Cyclin D1 is a chief regulator of the cell cycle and transcriptional processes . Among other human cancers, it is expressed in mantle cell lymphoma (MCL), where its encoding gene CCND1 is activated by the t(11;14)(q13;q32) in almost 100% of cases. Through an alternative splicing, CCND1 generates two mRNAs, cyclin D1a and D1b, which differ in their C-terminus. It is currently thought that cyclin D1b could represent a nuclear oncogene. In clinical practice, identification of cyclin D1 over-expression and/or t(11;14) is confirmatory for the diagnosis of MCL. Furthermore, cyclin D1 is over-expressed in approximately 25‚??50% of multiple myeloma (MM) patients, yet the t(11;14)(q13;q32) is only present in 3‚??14% of them . The relevance of cyclin D1 in pathogenesis of MCL and MM remains elusive ...

Near-tetraploidy clone can evolve from a hyperdiploidy clone and cause resistance to lenalidomide and bortezomib in a multiple myeloma patient

We report of a 55-year-old female patient diagnosed with advanced stage MM with hyperdiploidy and t(8;14)(q24;q32). The patient responded well to lenalidomide and dexamethasone for approximately 1 year. At the time of progression, she had become unresponsive to lenalidomide and subsequently bortezomib, and was found to have NT and loss of choromosome13. There is another reported patient who had a possible interchange from nonhyperdiploidy to hyperdiploidy status, however, artifact could not be ruled out. To our knowledge, this is the first patient in whom evolution of an abnormal clone from a hyperdiploidy to a NT abnormal clone has been confirmed during the natural course of MM. This evolution is associated with resistance to novel drugs and poor prognosis in MM. (Source: Leukemia Researc...

Treatment With Rituxan May Reduce Recurrence of Follicular Lymphoma

Research also finds Revlimid slows progression of multiple myeloma (Source: Pharmacy News - Doctors Lounge)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Treatment with Rituxan May Reduce Recurrence of Follicular Lymphoma

Research also finds Revlimid slows progression of multiple myeloma Source: HealthDay Related MedlinePlus Pages: Lymphoma, Multiple Myeloma (Source: MedlinePlus Health News)

Celgene's Revlimid positive in maintenance trials

BOSTON (Reuters) - Two major studies of Celgene Corp's multiple myeloma drug Revlimid showed that when taken as maintenance therapy following stem cell transplantation it reduced the risk of disease progression by more than 50 percent. (Source: Reuters: Health)

Importance of Achieving a Complete Response in Multiple Myeloma, and the Impact of Novel Agents [REVIEW ARTICLE]

The goal of treatment for multiple myeloma (MM) is to improve patients' long-term outcomes. One important factor that has been associated with prolonged progression-free and overall survival is the quality of response to treatment, particularly achievement of a complete response (CR). There is extensive evidence from clinical studies in the transplant setting in first-line MM demonstrating that CR or maximal response post-transplant is significantly associated with prolonged progression-free and overall survival, with some studies demonstrating a similar association with postinduction response. Supportive evidence is also available from studies in the nontransplant and relapsed settings. With the introduction of bortezomib, thalidomide, and lenalidomide, higher rates of CR are being achiev...

Plerixafor (Mozobil) for stem cell mobilization in patients with multiple myeloma previously treated with lenalidomide

Authors: I N M Micallef, A D Ho, L M Klein, S Marulkar, P J Gandhi & P A McSweeney (Source: Bone Marrow Transplantation)

Therapeutic approaches for newly diagnosed multiple myeloma patients in the era of novel drugs

The treatment of newly diagnosed multiple myeloma (MM) has evolved rapidly over recent years. The availability of new effective drugs with novel mechanisms of action, such as thalidomide, lenalidomide and bortezomib in the last decade, has resulted in a new scenario expected to impact favorably on the outcome of patients with MM. The introduction of new drugs in the treatment of patients eligible for autologous stem cell transplantation (ASCT) has allowed for a significant increase of complete response rate with a positive impact on progression-free survival. In patients not eligible for ASCT, randomized trials have shown that both thalidomide and bortezomib when combined with melphalan and prednisone (MP) are superior to MP and are now considered the standard of care. Ongoing trials are a...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Changes in RPS14 expression levels during lenalidomide treatment in Low- and Intermediate-1-risk myelodysplastic syndromes with chromosome 5q deletion

Conclusions: These observations in the patient setting support the importance of RPS14 in the pathogenesis of MDS with del(5q). (Source: European Journal of Haematology)

Management of disease- and treatment-related complications in patients with multiple myeloma

Abstract&nbsp;&nbsp;Treatment of myeloma has dramatically changed after introduction of novel agents, such as thalidomide, lenalidomide and bortezomib, with a significant improvement in response rate and survival of patients with myeloma. For newly diagnosed patients not eligible for transplant, the standards of care are now considered melphalan and prednisone (MP) plus thalidomide and MP plus bortezomib. Ongoing randomized trials are evaluating lenalidomide plus MP and lenalidomide plus dexamethasone. For newly diagnosed patients eligible for transplant, new induction regimens included the combination of high-dose dexamethasone plus thalidomide, high-dose dexamethasone plus lenalidomide (RD) and high-dose dexamethasone plus bortezomib (VD). The combinations RD, VD and bortezomib plu...

The quality of response to lenalidomide plus dexamethasone is associated with improved clinical outcomes in patients with relapsed or refractory multiple myeloma.

ConclusionsContinuing treatment with lenalidomide plus dexamethasone to achieve best response, in the absence of disease progression and toxicity, provided deeper remissions and greater clinical benefit over time for patients in this study. PMID: 20460639 [PubMed - as supplied by publisher] (Source: Haematologica)

SMC accepts restricted use of lenalidomide (Revlimid¬ģ) for multiple myeloma

Source: Scottish Medicines Consortium (SMC) Area: Evidence > Drug Specific Reviews Following a re-submission, the Scottish Medicines Consortium (SMC) has accepted for restricted use within NHS Scotland, lenalidomide (Revlimid¬ģ) for the treatment of multiple myeloma patients who have received at least one prior therapy. &nbsp; Use should be restricted to patients who have received at least two prior lines of therapy. The Committee added that taking into account the orphan drug status of lenalidomide and the substantial survival benefit it appears to offer in this patient group, the economic case was demonstrated. (Source: NeLM - Drug Specific Reviews)

Integrating novel agents into multiple myeloma treatment - current status in Switzerland and treatment recommendations.

This article summarises the discussions of an expert meeting which was held to debate current treatment practices for multiple myeloma in Switzerland concerning the role of the novel agents and to provide recommendations for their use in different treatment stages based on currently available clinical data. Novel agent combinations for the treatment of newly diagnosed, as well as relapsed multiple myeloma are examined. In addition, the role of novel agents in patients with cytogenetic abnormalities and renal impairment, as well as the management of the most frequent side effects of the novel agents are discussed. The aim of this article is to assist in treatment decisions in daily clinical practice to achieve the best possible outcome for patients with multiple myeloma. PMID: 20458652 ...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Lenalidomide plus dexamethasone vs. lenalidomide plus melphalan and prednisone: a retrospective study in newly diagnosed elderly myeloma

Conclusions: Results show that both MPR and len/dex are efficacious regimens for elderly patients with myeloma. Randomized trials are needed to confirm these results. (Source: European Journal of Haematology)

Lenalidomide: Acneiform folliculitis in an elderly patient: case report

(Source: Reactions)

Lenalidomide: Autoimmune haemolytic anaemia: case report

(Source: Reactions)

Phase I Combination Trial of Lenalidomide and Azacitidine in Patients With Higher-Risk Myelodysplastic Syndromes [Hematologic Malignancies]

Conclusion The combination of lenalidomide and azacitidine is well tolerated with encouraging clinical activity. The go-forward dose is azacitidine 75 mg/m2 on days 1 through 5 and lenalidomide 10 mg on days 1 through 21. (Source: Journal of Clinical Oncology)

Bortezomib Plus Melphalan and Prednisone Compared With Melphalan and Prednisone in Previously Untreated Multiple Myeloma: Updated Follow-Up and Impact of Subsequent Therapy in the Phase III VISTA Trial [Hematologic Malignancies]

Conclusion VMP significantly prolongs OS versus MP after lengthy follow-up and extensive subsequent antimyeloma therapy. First-line bortezomib use does not induce more resistant relapse. VMP used upfront appears more beneficial than first treating with conventional agents and saving bortezomib- and other novel agent&ndash;based treatment until relapse. (Source: Journal of Clinical Oncology)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Lenalidomide for multiple myeloma

Nature Reviews Clinical Oncology 7, 241 (2010). doi:10.1038/nrclinonc.2010.55 Author: Lisa Hutchinson Previous studies have shown that thalidomide plus high-dose dexamethasone (thal/dex) has significant activity in patients with newly diagnosed multiple myeloma (MM), but does not improve survival compared with high-dose dexamethasone; therefore, better agents are needed. Superior outcomes for lenalidomide plus high-dose dexamethasone (len/dex) compared with (Source: Nature Clinical Practice Oncology)

Safety and efficacy of a combination therapy with Revlimid, Adriamycin and dexamethasone (RAD) in relapsed/refractory multiple myeloma (MM): a single-centre experience

Stem cell collection in patients with multiple myeloma: impact of induction therapy and mobilization regimen

Authors: A Nazha, R Cook, D T Vogl, P A Mangan, M Gardler, K Hummel, K Cunningham, S M Luger, D L Porter, S Schuster, U O'Doherty, D Siegel & E A Stadtmauer (Source: Bone Marrow Transplantation)

AACR: Drug Combo Effective in Cancer Models (CME/CE)

WASHINGTON (MedPage Today) -- Researchers suggest that the combination of the thalidomide analogue, lenalidomide (Revlimid) and the taxane docetaxel (Taxotere) may be able to improve survival in cell and animal models of hormone-resistant metastatic prostate cancer. (Source: MedPage Today Hematology/Oncology)

Oral Ezatiostat HCl (TLK199) and Myelodysplastic syndrome: A case report of sustained hematologic response following an abbreviated exposure

Treatment options for patients with lower risk non-del(5q) myelodysplastic syndromes (MDS) who fail erythroid stimulating agents are restricted to one of the hypomethylating drugs with an expected response rate of ~50%. Ezatiostat HCl, an agent with the potential for producing multi-lineage responses in this population is currently in clinical investigation phase. This case report describes a 77 year old male who received less than two cycles of therapy with ezatiostat HCl which had to be aborted due to intolerable side effects, but which produced a sustained normalization of all three blood counts. This trilineage response has now lasted for more than a year. Interestingly, the patient began with a del(5q) abnormality and responded briefly to lenalidomide. Upon relapse of the anemia, a bo...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Novel agents and regimens for acute myeloid leukemia: 2009 ASH annual meeting highlights

Prognostic markers, such as NPM1, Flt3-ITD, and cytogenetic abnormalities have made it possible to formulate aggressive treatment plans for unfavorable acute myeloid leukemia (AML). However, the long-term survival of AML with unfavorable factors remains unsatisfactory. The latest data indicate that the standard dose of daunorubicin (DNR) at 45mg/m2 is inferior to high dose 90 mg/m2 for induction therapy. The rates of complete remission and overall survival are significantly better in the high dose induction regimen. New regimens exploring the new liposomal encapsulation of Ara-C and DNR as well as addition of gemtuzumab ozogamicin monoclonal antibody have been studied. New agents, including the nucleoside analogues (clofarabine, sapacitabine, elacytarabine), FLT3 inhibitor (sorafenib), far...

The oral histone deacetylase inhibitor LBH589 is a potential and promising therapeutic agent in multiple myeloma after at least two lines of chemotherapy including bortezomib or lenalidomide.

CONCLUSIONS: LBH589 may be very effective in multiple myeloma after a multitude of preceding treatments that could not induce a long-term anti-myeloma effect. Future trials with LBH589 should search for the specific characteristics of responding patients. PMID: 20389145 [PubMed - in process] (Source: Onkologie)

Venous thromboembolism in multiple myeloma: Current perspectives in pathogenesis

Abstract: Patients with multiple myeloma are at increased risk of venous thromboembolism (VTE) compared to the general population. The introduction of immunomodulatory agents, such as thalidomide and lenalidomide, substantially increases the incidence of VTE in multiple myeloma patients, especially when used in combination with high-dose dexamethasone and/or anthracycline-based chemotherapy. Thromboprophylaxis is recommended for reducing VTE in patients receiving immunomodulatory agent-based regimens. On the other hand, bortezomib, a proteasome inhibitor, is not associated with an increased risk of VTE, as observed by a very low incidence of thrombotic complications in the absence of thromboprophylaxis. Currently, the mechanisms underlying the impact of these agents on VTE are not well-und...

Lenalidomide, melphalan, prednisone and thalidomide (RMPT) for relapsed/refractory multiple myeloma

Lenalidomide, melphalan, prednisone and thalidomide (RMPT) for relapsed&#47;refractory multiple myeloma Leukemia advance online publication, April 8, 2010. doi:10.1038/leu.2010.58 Authors: A Palumbo, A Larocca, P Falco, G Sanpaolo, A P Falcone, V Federico, L Canepa, M Crugnola, M Genuardi, V Magarotto, M T Petrucci & M Boccadoro (Source: Leukemia)

Lenalidomide treatment promotes CD154 expression on CLL cells and enhances production of antibodies by normal B cells through a PI3-kinase-dependent pathway

This study is registered at http://clinicaltrials.gov as NCT00466895. (Source: Blood)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Lenalidomide for Treatment of Myelodysplastic Syndromes: Current Status and Future Directions

Lenalidomide was approved by the US Food and Drug Administration (FDA) for treatment of transfusion-dependent lower-risk myelodysplastic syndrome patients with deletion (del) (5q) alone or with additional karyotype abnormalities. The approval was based on high rates of prolonged transfusion independence and complete cytogenetic response in this subset. In lower-risk non-del(5q) patients, meaningful erythroid responses also were reported with a low frequency of cytogenetic improvement, although inferior to that observed in the del(5q) patients. There is now a better understanding of the mechanism of the karyotype-dependent drug action, explaining the disparate response rates and frequency of myelosuppression. In del(5q) patients, lenalidomide suppresses the clone by inhibiting the nuclear s...

Hematology: NPI-0052 and lenalidomide trigger apoptosis in multiple myeloma cells

Nature Reviews Clinical Oncology 7, 182 (2010). doi:10.1038/nrclinonc.2010.22 Author: Rowan Higgs Recent evidence indicates that the novel 20S proteasome inhibitor NPI-0052 (Marizomib) triggers apoptosis in multiple myeloma (MM) cells, when given in combination with the immunomodulatory agent lenalidomide. This is significant because NPI-0052 might offer a novel therapeutic option for patients resistant to bortezomib and lenalidomide. (Source: Nature Clinical Practice Oncology)

Renal recovery with lenalidomide in a patient with bortezomib-resistant multiple myeloma

Authors: Heinz Ludwig & Niklas Zojer Background. A 51-year-old man presented with an 8&#160;month history of migratory pain and weakness.Investigations. Conventional X-ray, MRI, laboratory investigations including serum electropheresis and immunofixation, measurement of the glomerular filtration rate and levels of serum creatinine and lactate dehydrogenase, and 24 h urine (Source: Nature Clinical Practice Oncology)

Stem cell transplantation in multiple myeloma: impact of response failure with thalidomide or lenalidomide induction

Autologous stem cell transplantation as a platform for multiple myeloma treatment is the standard of care for patients who can safely withstand the procedure. Before novel agents were introduced, one-third to one-half of patients did not achieve partial response at transplantation. Previous medical literature has shown that in this past era, absence of initial response to induction therapy had no impact on progression-free survival and overall survival after high-dose therapy. Lack of response to initial induction did not preclude a good response after stem cell transplantation. With the introduction of novel agents&mdash;immunomodulatory drugs and proteasome inhibitors&mdash;response rates with initial therapy are now between 70% and 100%. This retrospective study analyzes progression-fre...

Multiple myeloma: chemotherapy or transplantation in the era of new drugs

Conclusions: The incorporation of new drugs as induction therapy along with ASCT appears to produce very good partial response rates, slightly superior to those achieved by conventional chemotherapy with new drugs. How to best optimize induction, consolidation, and maintenance therapy and how to best select and prepare patients for ASCT are still to be determined. Randomized trials are needed to directly compare the current best chemotherapeutic approach with best ASCT strategies and to guide clinical practice for patients with MM. (Source: European Journal of Haematology)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

EVITA: a tool for the early EValuation of pharmaceutical Innovations with regard to Therapeutic Advantage

Conclusions: The strength of EVITA appears to lie in its speedy assessment of the potential therapeutic advantage of a new drug for a given indication. At the same time, this approach draws attention to the typical deficits of data used for drug approval. EVITA is not intended to replace classical health technology assessment reports but rather serves as a screening tool in the sense of horizon scanning. (Source: BioMed Central)

Response to lenalidomide in patients with myelodysplastic syndrome with deletion 5q: clinical and cytogenetic analysis of a single centre series

Content Type Journal ArticleCategory Letter to the EditorDOI 10.1007/s00277-010-0932-2Authors Rita Coutinho, University of Barcelona Institute of Hematology and Oncology, Department of Hematology, Hospital Clinic IDIBAPS Villarroel 170 08036 Barcelona SpainDolors Costa, University of Barcelona Hematopathology Unit, Hospital Clinic IDIBAPS Barcelona SpainAna Carri√≥, University of Barcelona Hematopathology Unit, Hospital Clinic IDIBAPS Barcelona SpainConcha Mu√Īoz, University of Barcelona Hematopathology Unit, Hospital Clinic IDIBAPS Barcelona SpainAna Vidal, University of Barcelona Hematopathology Unit, Hospital Clinic IDIBAPS Barcelona SpainMohammed Belkaid, University of Barcelona Institute of Hematology and Oncology, Department of Hematology, Hospital Clinic IDIBAPS Villarroel 170 0...

Blockade of the MEK/ERK signalling cascade by AS703026, a novel selective MEK1/2 inhibitor, induces pleiotropic anti-myeloma activity in vitro and in vivo

This study investigated the cytotoxicity and mechanism of action of AS703026, a novel, selective, orally bioavailable MEK1/2 inhibitor, in human multiple myeloma (MM). AS703026 inhibited growth and survival of MM cells and cytokine-induced osteoclast differentiation more potently (9- to 10-fold) than AZD6244. Inhibition of proliferation induced by AS703026 was mediated by G0-G1 cell cycle arrest and was accompanied by reduction of MAF oncogene expression. AS703026 further induced apoptosis via caspase 3 and Poly ADP ribose polymerase (PARP) cleavage in MM cells, both in the presence or absence of bone marrow stromal cells (BMSCs). Importantly, AS703026 sensitized MM cells to a broad spectrum of conventional (dexamethasone, melphalan), novel or emerging (lenalidomide, perifosine, bortezomib...

Advances in treatment for relapses and refractory multiple myeloma

This article will review the current role for thalidomide, lenalidomide, and bortezomib-based combinations, as well as some preliminary findings for promising investigational agents currently in clinical trials for patients with relapsed and/or refractory disease. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s12032-009-9407-5Authors Tiffany Richards, MD Anderson Cancer Center Houston TX USADonna Weber, MD Anderson Cancer Center Houston TX USA Journal Medical OncologyOnline ISSN 1559-131XPrint ISSN 1357-0560 (Source: Medical Oncology)

Best Practices in the Management of Newly Diagnosed Multiple Myeloma Patients Who Will Not Undergo Transplant

No survival advantage of autologous stem cell transplantation (ASCT) has been documented for patients older than 65 years, and in the era of thalidomide (Thalomid), bortezomib (Velcade), and len­alidomide (Revlimid), ASCT has a diminished role in the front-line treatment of older patients with myeloma. (Source: Cancer Network)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

More Biotech Buyout or M&A Targets (OSIP, VRTX, AUXL, ITMN, HGSI, CELG, DNDN, ENZN, FACT, PBE, XBI)

After today&#8217;s hostile Astellas offer for OSI Pharmaceuticals (NASDAQ: OSIP), we have investors and traders alike looking for &#8216;the next takeover target&#8217; in biotech.  Buy now you know that there are many pitfalls in simply looking for biotech stocks to buy because they will be taken over.  We have taken a look through our own recent stocks noted as takeover candidates and even gone through some sites of our partners looking through potential takeover candidates in the space. Morningstar just last week had a short video with some key potential buyout targets in the biotech space.  It noted Vertex Pharmaceuticals Incorporated (NASDAQ: VRTX), Auxilium Pharmaceuticals Inc. (NASDAQ: AUXL), and InterMune Inc. (NASDAQ: ITMN).  Those are all names that have come up as takeout t...

Rhabdomyolysis and Pandemic (H1N1) 2009 Pneumonia in Adult.

Authors: Gutierrez RL, Ellis MW, Decker CF To the Editor: A 56-year-old man came to the emergency department (ED) of Malcolm Grow Medical Center at Andrews Air Force Base in suburban Maryland, USA, just outside Washington, DC. He had a history of several days of cough, fever, and malaise; was a nonsmoker; was overweight (body mass index 28 kg/m2); and did not have chronic pulmonary disease. Radiographs showed bilateral pulmonary infiltrates, and he was hypoxemic. Two weeks previously, the patient had begun receiving therapy for recurrent multiple myeloma (lenalidomide and high-dose dexamethasone). He was intubated at the time of initial visit to the ED for influenza symptoms, and broad-spectrum antimicrobial drugs were administered (vancomycin 1,000 mg every 12 h, piperacillin-tazobact...

[Elderly patients with myelodysplastic syndrome with del 5q receiving lenalidomide: two case reports with poor prognosis.]

We report two cases of myelodysplastic syndrome (MDS) with del(5q) isolated cytogenetic abnormality in elderly patients: AREB-1 in Patient 1, "5q syndrome" in Patient 2. A first line of treatment including hematopoietic growth factors (darbepoetin alone or associated with G-CSF) failed after several months and a treatment with lenalidomide was initiated in both cases. The treatment was poorly tolerated (myelosuppression) in Patient 1 without an improvement of the quality of life; a progression of the disease was observed with an increase of the bone marrow blastosis and a new acquired karyotypic abnormality (t13;17), leading to the prescription of 5-azacytidine. Patient 2 had a good response to lenalidomide for several months with an increase in the haemoglobin level and a transfusion inde...

Therapy of chronic lymphocytic leukaemia

Rapid progress has been achieved recently in the management of chronic lymphocytic leukaemia (CLL). New insights into the molecular pathology of CLL have generated a plethora of biological markers that predict the prognosis and influence therapeutic decisions. Moreover, fludarabine, bendamustine and two monoclonal antibodies, alemtuzumab and rituximab, have been approved by European and/or American regulatory agencies. Additional monoclonal antibodies targeting CD20, CD23, CD37, CD38 or CD40, as well as drugs designed to interfere with proteins regulating the cell cycle, apoptotic machinery or leukaemic microenvironment (e.g., flavopiridol, oblimersen, ABT-263 or lenalidomide) are investigated in clinical trials. An increased experience with reduced-intensity allogeneic progenitor cell tra...

Lenalidomide-Induced Interstitial Lung Disease

We describe a 73-year-old woman who received lenalidomide therapy for multiple myeloma. Nine weeks after starting the drug, she developed progressive dyspnea, cough, and constitutional symptoms, and was found to be hypoxic. A computed tomography scan of the chest showed bilateral interstitial infiltrates. Bronchoalveolar lavage was negative for infection, but transbronchial biopsy showed an organizing pneumonia. The patient was diagnosed with lenalidomide-induced interstitial lung disease after other causes were excluded. Clinical and radiologic resolution occurred after lenalidomide was discontinued and a tapering course of corticosteroids was begun. Use of the Naranjo adverse drug reaction probability indicated a high probability (score of 7) that this adverse drug reaction was caused by...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Lenalidomide: Tumour flare reactions and other toxicities: 3 case reports

(Source: Reactions)

Lenalidomide and dexamethasone for the treatment of refractory/relapsed multiple myeloma: dosing of lenalidomide according to renal function and effect on renal impairment

Conclusions: We conclude that LenDex is an active treatment even in heavily pretreated MM. With dosing of lenalidomide according to renal function, LenDex can be administered to patients with RI (who may not have other treatment options) without excessive toxicity. Furthermore, LenDex may improve the renal function in approximately 40% of patients with RI. (Source: European Journal of Haematology)

The evolution and impact of therapy in multiple myeloma

Abstract&nbsp;&nbsp;Multiple myeloma is a clonal B-cell malignancy characterized by aberrant expression of plasma cells wtihin the bone marrow, and is associated with the well known clinical manifestations anemia, bone disease, renal dysfunction, hypercalcemia, and recurrent infections. For many years, melphalan and prednisone represented the standard of care in multiple myeloma therapy, with stem cell transplantation reserved for selected patients. Treatment of the disease has evolved rapidly over the past decade, however, with the development and utilization of thalidomide, lenalidomide, and bortezomib. As a result of these developments, clinical outcomes have improved significantly. This review highlights important historic landmarks as well as more recent events that have played ...

Lenalidomide plus dexamethasone versus thalidomide plus dexamethasone in newly diagnosed multiple myeloma: a comparative analysis of 411 patients

The objective of this case-control study was to compare the efficacy and toxicity of lenalidomide plus dexamethasone (len/dex) versus thalidomide plus dexamethasone (thal/dex) as initial therapy for newly diagnosed myeloma. We retrospectively studied 411 newly diagnosed patients treated with len/dex (228) or thal/dex (183) at the Mayo Clinic. The differences were similar in a matched-pair analysis that adjusted for age, sex, transplantation status, and dexamethasone dose. The proportions of patients achieving at least a partial response to len/dex and thal/dex were 80.3% versus 61.2%, respectively (P &lt; .001); very good partial response rates were 34.2% and 12.0%, respectively (P &lt; .001). Patients receiving len/dex had longer time to progression (median, 27.4 vs 17.2 months; P = .019)...

Revlimid 5, 10, 15, 25mg capsules (lenalidomide) - Revised SPC

Source: eMC (electronic Medicines Compendium) Area: Other Library Updates > SPC Changes ??In section 4.4 (Special warnings and precautions for use), new data on the presence of lenalidomide in human semen "at extremely low levels" has been added. In the section entitled: Additional precautions, the precaution regarding semen donation during or 1 week following discontinuation of therapy has been removed, however the precaution regarding blood donation remains. In section 5.1 (Pharmacodynamic properties) extended follow up data has been added regarding the MM 009 and MM 010 studies. In section 5.3 (Preclinical safety data) more detail regarding the findings of an embryofoetal malformation study conducted in monkeys has been added. (Source: NeLM - SPC Changes)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Distribution of Lenalidomide Into Semen of Healthy Men After Multiple Oral Doses.

Authors: Chen N, Lau H, Choudhury S, Wang X, Assaf M, Laskin OL Lenalidomide is a thalidomide analog and an immunomodulatory drug with demonstrated efficacy in various hematological malignancies. The distribution of lenalidomide into semen was evaluated in healthy subjects. Twenty-four male subjects were randomized into 4 equal groups for semen collection. All subjects received lenalidomide 25 mg once daily for 4 days. After the last dose, a single semen sample was collected from subjects, at approximately 2, 24, 72, and 168 hours for groups 1, 2, 3, and 4, respectively, and serial blood sampling was performed for 24 hours in all groups. The mean lenalidomide concentration in semen was 478 ng/mL at 2 hours and 10.0 ng/mL at 24 hours, which was higher than was the corresponding drug con...

CD19 targeting of chronic lymphocytic leukemia with a novel Fc-domain-engineered monoclonal antibody

CD19 is a B cell&ndash;specific antigen expressed on chronic lymphocytic leukemia (CLL) cells but to date has not been effectively targeted with therapeutic monoclonal antibodies. XmAb5574 is a novel engineered anti-CD19 monoclonal antibody with a modified constant fragment (Fc)&ndash;domain designed to enhance binding of FcRIIIa. Herein, we demonstrate that XmAb5574 mediates potent antibody-dependent cellular cytotoxicity (ADCC), modest direct cytotoxicity, and antibody-dependent cellular phagocytosis but not complement-mediated cytotoxicity against CLL cells. Interestingly, XmAb5574 mediates significantly higher ADCC compared with both the humanized anti-CD19 nonengineered antibody it is derived from and also rituximab, a therapeutic antibody widely used in the treatment of CLL. The XmAb...

Bortezomib As Induction Before Autologous Transplantation, Followed by Lenalidomide As Consolidation-Maintenance in Untreated Multiple Myeloma Patients [Hematologic Malignancies]

Conclusion Bortezomib as induction before autologous transplantation, followed by lenalidomide as consolidation-maintenance, is an effective regimen. (Source: Journal of Clinical Oncology)

Constitutive down-regulation of Osterix in osteoblasts from myeloma patients: In vitro effect of Bortezomib and Lenalidomide

Abstract: Bortezomib and Lenalidomide have been shown to be effective in the control of multiple myeloma (MM) progression. We have investigated their role in the in vitro expression of Osterix by primary osteoblast cultures from MM patients and found that Osterix RNA was constitutively down-regulated in these cells. Treatment of osteoblasts with Bortezomib resulted in an increase of Osterix RNA and in enhanced activity of both BMP-2 and Runx2. Instead, Lenalidomide was unable to modify Osterix transcription. These findings provide additional evidence suggesting that, at least in vitro, Bortezomib promotes the osteoblast maturation whereas Lenalidomide is ineffective. (Source: Leukemia Research)

Incidence, presenting features and outcome of extramedullary disease in multiple myeloma: a longitudinal study on 1003 consecutive patients

Conclusions: The incidence of EM disease has increased, probably due to the availability of more sensitive imaging techniques and the prolongation of patients&rsquo; survival. HDT or novel agents seem not to increase the risk of EM disease. EM involvement confers a poor prognosis. (Source: Annals of Oncology)<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Combination of novel proteasome inhibitor NPI-0052 and lenalidomide trigger in vitro and in vivo synergistic cytotoxicity in multiple myeloma

Our recent study demonstrated that a novel proteasome inhibitor NPI-0052 is distinct from bortezomib (Velcade) and, importantly, triggers apoptosis in multiple myeloma (MM) cells resistant to bortezomib. Here we demonstrate that combining NPI-0052 and lenalidomide (Revlimid) induces synergistic anti-MM activity in vitro using MM-cell lines or patient MM cells. NPI-0052 plus lenalidomide-induced apoptosis is associated with (1) activation of caspase-8, caspase-9, caspase-12, caspase-3, and poly(ADP) ribose polymerase; (2) activation of BH-3 protein BIM; (3) translocation of BIM to endoplasmic reticulum; (4) inhibition of migration of MM cells and angiogenesis; and (5) suppression of chymotrypsin-like, caspase-like, and trypsin-like proteasome activities. Importantly, blockade of BIM using s...

Celgene Sees 4Q Profit On Sales Boost, Lower Costs

From Associated Press (January 28, 2010) SUMMIT, N.J.--Biotech drugmaker Celgene Corp. on Thursday reported a fourth-quarter profit on a boost in sales of the cancer drugs Revlimid and Vidaza, along with lower research and development costs. The... (Source: Drugs.com - Pharma News)

Infections frequent with lenalidomide

(Source: Reactions)

Immunomodulatory derivatives induce PU.1 down-regulation, myeloid maturation arrest, and neutropenia

The immunomodulatory drugs (IMiDs) lenalidomide and pomalidomide yield high response rates in patients with multiple myeloma, but the use of IMiDs in multiple myeloma is associated with neutropenia and increased risk for venous thromboembolism (VTE) by mechanisms that are unknown. We show that IMiDs down-regulate PU.1, a key transcription factor involved in granulocyte differentiation in vitro and in patients treated with lenalidomide. Loss of PU.1 results in transient maturation arrest with medullary accumulation of immature myeloid precursors and subsequent neutropenia. Accumulation of promyelocytes leads to high levels of the platelet aggregation agonist, cathepsin G stored in the azurophilic granules of promyelocytes. High levels of cathepsin G subsequently may increase the risk of VTE...

Current Multiple Myeloma Treatment Strategies with Novel Agents: A European Perspective.

Authors: Ludwig H, Beksac M, Blad&#xE9; J, Boccadoro M, Cavenagh J, Cavo M, Dimopoulos M, Drach J, Einsele H, Facon T, Goldschmidt H, Harousseau JL, Hess U, Ketterer N, Kropff M, Mendeleeva L, Morgan G, Palumbo A, Plesner T, San Miguel J, Shpilberg O, Sondergeld P, Sonneveld P, Zweegman S The treatment of multiple myeloma (MM) has undergone significant developments in recent years. The availability of the novel agents thalidomide, bortezomib, and lenalidomide has expanded treatment options and has improved the outcome of patients with MM. Following the introduction of these agents in the relapsed/refractory setting, they are also undergoing investigation in the initial treatment of MM. A number of phase III trials have demonstrated the efficacy of novel agent combinations in the transp...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

BOPA standards for clinical pharmacy verification of prescriptions for cancer medicines

Source: BOPA website Area: News The British Oncology Pharmacy Association (BOPA) has produced a set of standards, describing what key steps a pharmacist must take when checking prescriptions for anticancer medicines.&nbsp; This will allow all Chemotherapy Services to assure themselves that their pharmacy policies, procedures and practices meet the required standard. &nbsp; This guidance applies to parenteral and oral administration of systemic anticancer therapies, including chemotherapy and non-cytotoxic medicines such as targeted therapies, antibody treatments and novel therapies (e.g. rituximab, sunitinib and lenalidomide).&nbsp; It is supplemented by a 'Supporting Guidance' document, which will provide more detailed guidance to assist pharmacists in undertaking each of the steps r...

Majestic Research Finds Hematologists/Oncologists Expect To Change Multiple Myeloma Treatment Practices Due To ASH 2009 Data

In a study published by Majestic Research's Market Research Group (formerly Rood Research), it was found that many hematologists and oncologists who attended the American Society of Hematology (ASH) 2009 Annual Meeting expect to change their multiple myeloma treatment practices, based on new data presented at the meeting. Of the hematologists and oncologists surveyed, 43% reported they expect to change their typical treatment protocol as a result of the meeting, with most planning to use more of either Revlimid, Velcade, or the two agents together in combination... (Source: Health News from Medical News Today)

Impact of high-risk cytogenetics and prior therapy on outcomes in patients with advanced relapsed or refractory multiple myeloma treated with lenalidomide plus dexaméthasone

Impact of high-risk cytogenetics and prior therapy on outcomes in patients with advanced relapsed or refractory multiple myeloma treated with lenalidomide plus dexam&#233;thasone Leukemia advance online publication, January 14, 2010. doi:10.1038/leu.2009.273 Authors: H Avet-Loiseau, J Soulier, J-P Fermand, I Yakoub-Agha, M Attal, C Hulin, L Garderet, K Belhadj, V Dorvaux, S Minvielle & P Moreau (Source: Leukemia)

Testing the NKT cell hypothesis in lenalidomide-treated myelodysplastic syndrome patients

Authors: A C Chan, P Neeson, E Leeansyah, K Tainton, H Quach, H M Prince, D I Godfrey, D Ritchie & S P Berzins (Source: Leukemia)

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