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https://www.readbyqxmd.com/read/28430175/carfilzomib-lenalidomide-dexamethasone-vs-lenalidomide-dexamethasone-in-relapsed-multiple-myeloma-by-previous-treatment
#1
M A Dimopoulos, A K Stewart, T Masszi, I Špička, A Oriol, R Hájek, L Rosiñol, D Siegel, G G Mihaylov, V Goranova-Marinova, P Rajnics, A Suvorov, R Niesvizky, A Jakubowiak, J San-Miguel, H Ludwig, S Ro, S Aggarwal, P Moreau, A Palumbo
Carfilzomib, a proteasome inhibitor, is approved as monotherapy and in combination with dexamethasone or lenalidomide-dexamethasone (Rd) for relapsed or refractory multiple myeloma. The approval of carfilzomib-lenalidomide-dexamethasone (KRd) was based on results from the randomized, phase 3 study ASPIRE (NCT01080391), which showed KRd significantly improved progression-free survival (PFS) vs Rd (median 26.3 vs 17.6 months; hazard ratio (HR)=0.690; P=0.0001). This subgroup analysis of ASPIRE evaluated KRd vs Rd by number of previous lines of therapy and previous exposure to bortezomib, thalidomide or lenalidomide...
April 21, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28429724/clonal-evolution-in-myelodysplastic-syndromes
#2
Pedro da Silva-Coelho, Leonie I Kroeze, Kenichi Yoshida, Theresia N Koorenhof-Scheele, Ruth Knops, Louis T van de Locht, Aniek O de Graaf, Marion Massop, Sarah Sandmann, Martin Dugas, Marian J Stevens-Kroef, Jaroslav Cermak, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Theo de Witte, Nicole M A Blijlevens, Petra Muus, Gerwin Huls, Bert A van der Reijden, Seishi Ogawa, Joop H Jansen
Cancer development is a dynamic process during which the successive accumulation of mutations results in cells with increasingly malignant characteristics. Here, we show the clonal evolution pattern in myelodysplastic syndrome (MDS) patients receiving supportive care, with or without lenalidomide (follow-up 2.5-11 years). Whole-exome and targeted deep sequencing at multiple time points during the disease course reveals that both linear and branched evolutionary patterns occur with and without disease-modifying treatment...
April 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28427509/efficacy-and-safety-of-bortezomib-thalidomide-and-lenalidomide-in-multiple-myeloma-an-overview-of-systematic-reviews-with-meta-analyses
#3
REVIEW
Patricia Melo Aguiar, Tácio de Mendonça Lima, Gisele Wally Braga Colleoni, Sílvia Storpirtis
This overview summarizes evidence for the efficacy and safety of bortezomib, thalidomide, and lenalidomide in patients with multiple myeloma. We searched the Medline, Scopus, and LILACS databases through August 2016, including systematic reviews with meta-analyses of randomized controlled trials assessing the efficacy and/or safety of bortezomib, thalidomide, or lenalidomide in patients with multiple myeloma. Two authors performed study selection, data extraction, and quality assessment using AMSTAR and GRADE instruments...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28426350/lenalidomide-maintenance-compared-with-placebo-in-responding-elderly-patients-with-diffuse-large-b-cell-lymphoma-treated-with-first-line-rituximab-plus-cyclophosphamide-doxorubicin-vincristine-and-prednisone
#4
Catherine Thieblemont, Hervé Tilly, Maria Gomes da Silva, Rene-Olivier Casasnovas, Christophe Fruchart, Franck Morschhauser, Corinne Haioun, Julien Lazarovici, Anida Grosicka, Aurore Perrot, Judith Trotman, Catherine Sebban, Dolores Caballero, Richard Greil, Koen van Eygen, Amos M Cohen, Hugo Gonzalez, Reda Bouabdallah, Lucie Oberic, Bernadette Corront, Bachra Choufi, Armando Lopez-Guillermo, John Catalano, Achiel Van Hoof, Josette Briere, Jose Cabeçadas, Gilles Salles, Philippe Gaulard, Andre Bosly, Bertrand Coiffier
Purpose The standard treatment of patients with diffuse large B-cell lymphoma (DLBCL) is rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Lenalidomide, an immunomodulatory agent, has shown activity in DLBCL. This randomized phase III trial compared lenalidomide as maintenance therapy with placebo in elderly patients with DLBCL who achieved a complete response (CR) or partial response (PR) to R-CHOP induction. Methods Patients with previously untreated DLBCL or other aggressive B-cell lymphoma were 60 to 80 years old, had CR or PR after six or eight cycles of R-CHOP, and were randomly assigned to lenalidomide maintenance 25 mg/d or placebo for 21 days of every 28-day cycle for 24 months...
April 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28425720/a-cereblon-modulator-cc-220-with-improved-degradation-of-ikaros-and-aiolos
#5
Mary E Matyskiela, Weihong Zhang, Hon-Wah Man, George Muller, Godrej Khambatta, Frans Baculi, Matthew Hickman, Laurie LeBrun, Barbra Pagarigan, Gilles Carmel, Chin-Chun Lu, Gang Lu, Mariko Riley, Yoshitaka Satoh, Peter Schafer, Thomas O Daniel, James Carmichael, Brian E Cathers, Philip P Chamberlain
The drugs lenalidomide and pomalidomide bind to the protein cereblon, directing the CRL4-CRBN E3 ligase toward the transcription factors Ikaros and Aiolos to cause their ubiquitination and degradation. Here we describe CC-220 (compound 6), a cereblon modulator in clinical development for systemic lupus erythematosis and relapsed/refractory multiple myeloma. Compound 6 binds cereblon with a higher affinity than lenalidomide or pomalidomide. Consistent with this, the cellular degradation of Ikaros and Aiolos is more potent and the extent of substrate depletion is greater...
April 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28423741/lenalidomide-and-the-risk-of-serious-infection-in-patients-with-multiple-myeloma-a-systematic-review-and-meta-analysis
#6
Li Ying, Tong YinHui, Zheng Yunliang, Haozhen Sun
The immunomodulatory drug lenalidomide is highly effective against newly diagnosed and relapsed/refractory multiple myeloma (MM), but serious and even fatal infections have been associated with its use. In this meta-analysis, we assessed the overall risk of infection to MM patients treated with lenalidomide. Eleven phase II or III clinical trials, comprising 3,210 subjects, were selected from the Embase, Pubmed, and Cochrane Library databases, from the Clinical Trial Registration website, and from meeting abstracts and virtual presentations at the American Society of Clinical Oncology...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422865/crystalglobulinemia-manifesting-as-chronic-arthralgia-and-acute-limb-ischemia-a-clinical-case-report
#7
Nobuya Abe, Tomoko Tomita, Miyuki Bohgaki, Hideki Kasahara, Takao Koike
RATIONALE: Crystalglobulinemia is a rare disease caused by monoclonal immunoglobulins, characterized by irreversible crystallization on refrigeration. It causes systemic symptoms including purpura, arthralgia, and vessel occlusive conditions to be exacerbated by exposure to cold. We report a patient with crystalglobulinemia associated with monoclonal gammopathy of undetermined significance (MGUS) manifesting as chronic arthralgia and recurrent acute arterial occlusion. PRESENTING CONCERNS: A 61-year-old man, who had been diagnosed with MGUS and who had arthralgia of unknown origin, presented with recurrent acute limb ischemia after surgical thromboembolectomy...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28409228/diagnosis-and-treatment-of-multiple-myeloma-in-germany-analysis-of-a-nationwide-multi-institutional-survey
#8
Maximilian Merz, Lenka Kellermann, Wolfram Poenisch, Hans-Joachim Tischler, Joern Kohnke, Wolfgang Knauf, Hartmut Goldschmidt
A nationwide, multi-institutional survey was performed in 2011 and 2015 to analyze routine practice for myeloma patients outside clinical trials in Germany. We contacted university hospitals, community hospitals, and office-based hematologists in order to enter clinical data from newly diagnosed and relapsed patients into an online platform. Complete datasets were available for 478 (2011) and 515 (2015) patients. While median age at diagnosis increased from 70 to 72 years, patients had fewer concomitant diseases (2011 61%; 2015 51%) and presented with equal performance status (ECOG 0-1, 2011 66%; 2015 68%)...
April 13, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28405846/cancer-specific-geriatric-assessment-and-quality-of-life-important-factors-in-caring-for-older-patients-with-aggressive-b-cell-lymphoma
#9
Karin Ribi, Stéphanie Rondeau, Felicitas Hitz, Ulrich Mey, Milica Enoiu, Thomas Pabst, Anastasios Stathis, Natalie Fischer, Kerri M Clough-Gorr
PURPOSE: To evaluate the efficacy and tolerability of chemotherapy, a geriatric assessment is recommended in elderly patients with cancer. We aimed to characterize and compare patients with aggressive lymphoma by objective response and survival status based on pre-treatment cancer-specific geriatric (C-SGA) and quality of life (QoL) assessments. METHODS: Patients not eligible for anthracycline-based first-line therapy or intensive salvage regimens completed C-SGA and QoL assessment before and after a rituximab-bendamustine-lenalidomide (R-BL) treatment in a phase II clinical trial...
April 13, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28399522/autologous-stem-cell-transplantation-in-multiple-myeloma-in-the-era-of-novel-drug-induction-a-retrospective-single-center-analysis
#10
Gabriela B Thoennissen, Dennis Görlich, Ulrike Bacher, Thomas Aufenberg, Anne-Christin Hüsken, Anna Antonia Hansmeier, Georg Evers, Jan-Henrik Mikesch, Fleur Fritz, Carsten Bokemeyer, Carsten Müller-Tidow, Matthias Stelljes, Rolf M Mesters, Utz Krug, Martin H Kropff, Nils H Thoennissen, Wolfgang E Berdel
Within this retrospective single-center study, we analyzed the survival of 320 multiple myeloma (MM) patients receiving melphalan high-dose chemotherapy (HDCT) and either single (n = 286) or tandem (n = 34) autologous stem cell transplantation (ASCT) from 1996 to 2012. Additionally, the impact of novel induction regimens was assessed. Median follow-up was 67 months, median overall survival (OS) 62 months, median progression-free survival (PFS) 33 months (95% CI 27-39), and treatment-related death (TRD) 3%. Multivariate analysis revealed age ≥60 years (p = 0...
April 12, 2017: Acta Haematologica
https://www.readbyqxmd.com/read/28399009/primary-effusion-lymphoma-current-concepts-and-management
#11
Nivedita Arora, Arjun Gupta, Navid Sadeghi
PURPOSE OF REVIEW: To summarize the current epidemiology, management, and outcomes of primary effusion lymphoma (PEL) and highlight possible future research efforts. RECENT FINDINGS: Cyclophosphamide, doxorubicin, vincristine, prednisone-based chemotherapy regimens alone or in combination with immunomodulatory agents (e.g., lenalidomide), or proteasome inhibitors (e.g., bortezomib), or targeted therapies, are commonly used to treat PEL. Highly active antiretroviral therapy should be continued or initiated in patients with HIV infection...
April 8, 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/28395565/regression-of-methotrexate-resistant-aids-related-primary-central-nervous-system-lymphoma-with-lenalidomide-plus-combination-anti-retroviral-therapy
#12
Neel K Gupta, Chia-Ching Wang, Gabriel N Mannis, John-Paul J Yu, James L Rubenstein
No abstract text is available yet for this article.
April 10, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28388253/lenalidomide-in-the-treatment-of-chronic-lymphocytic-leukemia
#13
Gilad Itchaki, Jennifer R Brown
Lenalidomide is an immunomodulatory drug (IMiD) with a unique mode of action (MOA) that may vary across disease-type. It is currently approved in multiple myeloma (MM), myelodysplastic syndrome (MDS) and mantle cell lymphoma (MCL), yet is also clinically active in a host of lymphoproliferative diseases, including chronic lymphocytic leukemia (CLL). Due to its protean effects on the immune system, lenalidomide may be particularly appealing in CLL, which is distinct in its ability to evade immune recognition and cause immunosuppression...
April 7, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28382147/gambogenic-acid-synergistically-potentiates-bortezomib-induced-apoptosis-in-multiple-myeloma
#14
Runzhe Chen, Hongming Zhang, Ping Liu, Xue Wu, Baoan Chen
Background: Although the introduction of protease inhibitor bortezomib (BTZ) and immunomodulatory agent lenalidomide has led to improved outcomes in patients with multiple myeloma (MM), the disease remains incurable. Gambogenic acid (GNA), a polyprenylated xanthone isolated from the traditional Chinese medicine gamboge, has been reported to have potent antitumor activity and can effectively inhibit the survival and proliferation of cancer. In this study, we hypothesized that GNA could synergistically potentiate BTZ-induced apoptosis of MM cells and that combining BTZ and GNA may provide a more effective approach to treat MM...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28381416/a-phase-2-3-multicenter-randomized-open-label-study-of-lenalidomide-vs-investigator-s-choice-in-patients-with-relapsed-or-refractory-diffuse-large-b-cell-lymphoma
#15
Myron S Czuczman, Marek Trněný, Andrew Davies, Simon Aj Rule, Kim Linton, Nina Wagner-Johnston, Randy D Gascoyne, Graham Slack, Pierre Brousset, David A Eberhard, Francisco J Hernandez-Ilizaliturri, Gilles Salles, Thomas E Witzig, Pier Luigi Zinzani, George W Wright, Louis M Staudt, Yandan Yang, P Michael Williams, Chih-Jian Lih, Jacqueline Russo, Anjan Thakurta, Patrick Hagner, Pierre Fustier, Dale Song, Ian D Lewis
PURPOSE: Randomized, multicenter, open-label, phase 2/3 trial investigating lenalidomide versus investigator's choice (IC) in relapsed/refractory diffuse large B-cell lymphoma (DLBCL). EXPERIMENTAL DESIGN: Patients with DLBCL who received ≥2 prior therapies were stratified by DLBCL subtype (germinal center B-cell [GCB] vs non-GCB; determined by immunohistochemistry [IHC]), then randomized 1:1 to lenalidomide (25 mg/day, 21 days of 28-day cycle) or IC (gemcitabine, rituximab, etoposide, or oxaliplatin)...
April 5, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28379796/lenalidomide-bortezomib-and-dexamethasone-with-transplantation-for-myeloma
#16
Michel Attal, Valerie Lauwers-Cances, Cyrille Hulin, Xavier Leleu, Denis Caillot, Martine Escoffre, Bertrand Arnulf, Margaret Macro, Karim Belhadj, Laurent Garderet, Murielle Roussel, Catherine Payen, Claire Mathiot, Jean P Fermand, Nathalie Meuleman, Sandrine Rollet, Michelle E Maglio, Andrea A Zeytoonjian, Edie A Weller, Nikhil Munshi, Kenneth C Anderson, Paul G Richardson, Thierry Facon, Hervé Avet-Loiseau, Jean-Luc Harousseau, Philippe Moreau
Background High-dose chemotherapy plus autologous stem-cell transplantation has been the standard treatment for newly diagnosed multiple myeloma in adults up to 65 years of age. However, promising data on the use of combination therapy with lenalidomide, bortezomib, and dexamethasone (RVD) in this population have raised questions about the role and timing of transplantation. Methods We randomly assigned 700 patients with multiple myeloma to receive induction therapy with three cycles of RVD and then consolidation therapy with either five additional cycles of RVD (350 patients) or high-dose melphalan plus stem-cell transplantation followed by two additional cycles of RVD (350 patients)...
April 6, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28374162/peripheral-blood-cytogenetics-allows-treatment-monitoring-and-early-identification-of-treatment-failure-to-lenalidomide-in-mds-patients-results-of-the-le-mon-5-trial
#17
Friederike Braulke, Xenia Schulz, Ulrich Germing, Esther Schuler, Uwe Platzbecker, Florian Nolte, Wolf-Karsten Hofmann, Aristoteles Giagounidis, Katharina Götze, Michael Lübbert, Richard F Schlenk, Julie Schanz, Ulrike Bacher, Arnold Ganser, Guntram Büsche, Anne Letsch, Philippe Schafhausen, Gesine Bug, Tim H Brümmendorf, Rainer Haas, Lorenz Trümper, Katayoon Shirneshan, Detlef Haase
Transfusion-dependent patients with low- or intermediate-1-risk myelodysplastic syndrome, <5% bone marrow (BM) blasts and isolated 5q-deletion received lenalidomide within the German MDS study group phase-II clinical trial LE-MON-5 (EudraCT:2008-001866-10) of the University of Duesseldorf, Germany. Cytogenetic monitoring was performed by chromosome banding analyses (CBA) of BM cells and fluorescence in situ hybridization (FISH) analyses of peripheral blood (PB) mononuclear CD34+ cells using extended probe panels...
April 3, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28373701/benefit-of-continuous-treatment-for-responders-with-newly-diagnosed-multiple-myeloma-in-the-randomized-first-trial
#18
N J Bahlis, A Corso, L-O Mugge, Z-X Shen, P Desjardins, A-M Stoppax, O Decaux, T de Revel, M Granell, G Marit, H Nahi, H Demuynck, S-Y Huang, S Basu, T H Guthrie, A Ervin-Haynes, J Marek, G Chen, T Facon
The phase 3, randomized FIRST trial investigating lenalidomide plus low-dose dexamethasone until disease progression (Rd continuous) vs melphalan, prednisone, and thalidomide for 12 cycles (MPT) and Rd for 18 cycles (Rd18) in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM) showed that Rd continuous prolonged progression-free survival and overall survival compared with MPT. A subanalysis of the FIRST trial was conducted to determine the benefits of Rd continuous in patients with NDMM based on depth of response...
April 4, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28370245/renal-outcomes-in-patients-with-al-amyloidosis-prognostic-factors-renal-response-and-the-impact-of-therapy
#19
Efstathios Kastritis, Maria Gavriatopoulou, Maria Roussou, Magdalini Migkou, Despina Fotiou, Dimitrios C Ziogas, Nikos Kanellias, Evangelos Eleutherakis-Papaiakovou, Ioannis Panagiotidis, Stavroula Giannouli, Erasmia Psimenou, Smaragdi Marinaki, Theofanis Apostolou, Hariklia Gakiopoulou, Anna Tasidou, Ioannis Papassotiriou, Evangelos Terpos, Meletios A Dimopoulos
A staging system for patients with renal AL amyloidosis, based on eGFR (<50 ml/min/1.73 m(2) ) and proteinuria (≥5gr/day) at diagnosis, as well as criteria for renal progression (≥25% eGFR reduction) and response (≥30% reduction of proteinuria without renal progression) were recently proposed. We validated these criteria in a cohort of 125 patients with renal AL amyloidosis, mostly treated with bortezomib or lenalidomide. We confirmed the prognostic value of the renal staging system but also identified the limitations of renal progression criteria which are based only on eGFR reduction...
March 28, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28367597/salvage-therapy-with-lenalidomide-containing-regimen-for-relapsed-refractory-castleman-disease-a-report-of-three-cases
#20
Xinping Zhou, Juying Wei, Yinjun Lou, Gaixiang Xu, Min Yang, Hui Liu, Liping Mao, Hongyan Tong, Jie Jin
Castleman disease (CD) is uncommon non-clonal lymphoproliferative disorder with unknown etiology. No standard therapy is recommended for relapsed/refractory CD patients, thus requiring development of novel experimental approaches. Our cohort of three adult patients with multicentric CD (MCD) were treated with refractory to traditional chemotherapy lenalidomide-containing regimens (10-25 mg lenalidomide perorally administered on days 1-21 in 28-day cycle) as second- to fourth-line treatment. Partial remission was achieved in first plasma-cell CD patient, who relapsed seven months after autologous hematopoietic stem cell transplantation and then failed to respond to four cycles of chemotherapy...
April 3, 2017: Frontiers of Medicine
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