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https://www.readbyqxmd.com/read/28747306/how-i-treat-new-agents-in-myeloma
#1
Philippe Moreau
At present, multiple classes of agents with distinct mechanisms of action are available for the treatment of patients with multiple myeloma (MM), including alkylators, steroids, immunomodulatory agents (IMiDs), proteasome inhibitors (PIs), histone deacetylase inhibitors (DACIs) and monoclonal antibodies (mAbs). Over the last 5 years, several new agents, such as the third-generation IMiD pomalidomide, the second generation PIs carfilzomib and ixazomib, the DACI panobinostat and two monoclonal antibodies, elotuzumab and daratumumab, have been approved, incorporated into clinical guidelines and have transformed our approach to the treatment of patients...
July 26, 2017: Blood
https://www.readbyqxmd.com/read/28744161/emerging-combination-therapies-for-the-management-of-multiple-myeloma-the-role-of-elotuzumab
#2
REVIEW
Wei-Chih Chen, Abraham S Kanate, Michael Craig, William P Petros, Lori A Hazlehurst
Treatment options for patients with multiple myeloma (MM) have increased during the past decade. Despite the significant advances, challenges remain on which combination strategies will provide the optimal response for any given patient. Defining optimal combination strategies and corresponding companion diagnostics, that will guide clinical decisions are required to target relapsed or refractory multiple myeloma (RRMM) in order to improve disease progression, survival and quality of life for patients with MM...
2017: Cancer Management and Research
https://www.readbyqxmd.com/read/28734795/monoclonal-antibodies-in-multiple-myeloma-a-new-wave-of-the-future
#3
REVIEW
Daniel W Sherbenou, Tomer M Mark, Peter Forsberg
In 2015, 2 monoclonal antibodies were approved for the treatment of relapsed or refractory multiple myeloma (RRMM), elotuzumab and daratumumab. Elotuzumab is a monoclonal IgG-κ antibody directed against SLAMF7 (signaling lymphocytic activation molecule F7), a cell surface receptor involved in natural killer cell activation. Daratumumab is a monoclonal IgG-κ antibody that binds to CD38, a transmembrane protein found on the surface of myeloma cells and responsible for cellular adhesion and ectoenzymatic activity...
June 27, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28723635/meta-analysis-of-the-efficacy-of-treatments-for-newly-diagnosed-and-relapsed-refractory-multiple-myeloma-with-del-17p
#4
Jinghua Liu, Hui Yang, Xiaochan Liang, Yuxin Wang, Jian Hou, Yanqin Liu, Jigang Wang, Fan Zhou
We analyzed the treatment of newly diagnosed and relapsed/refractory multiple myeloma (NDMM/RRMM) patients with del(17p). Thirteen prospective studies that evaluated 3,187 MM patients, including 685with del(17p), were included in our meta-analysis. The incidence of del(17p) in NDMM and RRMM patients was similar (13% vs. 14%, respectively, P = 0.64, I2 = 94%). The overall response rate (ORR) to new agents was 40.5% and 67.1%, respectively, in RRMM patients with or without del(17p) (P = 0.1, I2 = 63.9%). NDMM patients with del(17p) treated with PAD (bortezomib, adriamycin, and dexamethasone) induction therapy followed by bortezomib maintenance therapy had higher progression-free survival (PFS) (25...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28679737/how-i-treat-first-relapse-of-myeloma
#5
Jean Luc Harousseau, Michel Attal
The standard treatment of relapsed multiple myeloma (MM) was either lenalidomide-dexamethasone (RD) or bortezomib-dexamethasone (VD) but it is changing rapidly for two reasons. Firstly lenalidomide and bortezomib are currently used in frontline treatment and many patients become resistant to these agents early in the course of their disease. Secondly six second-line new agents have been recently developed and offer new possibilities (pomalidomide, carfilzomib and ixazomib, panobinostat, elotuzumab and daratumumab)...
July 5, 2017: Blood
https://www.readbyqxmd.com/read/28677826/elotuzumab-plus-lenalidomide-dexamethasone-for-relapsed-or-refractory-multiple-myeloma-eloquent-2-follow-up-and-post-hoc-analyses-on-progression-free-survival-and-tumour-growth
#6
Meletios A Dimopoulos, Sagar Lonial, Darrell White, Philippe Moreau, Antonio Palumbo, Jesus San-Miguel, Ofer Shpilberg, Kenneth Anderson, Sebastian Grosicki, Ivan Spicka, Adam Walter-Croneck, Hila Magen, Maria-Victoria Mateos, Andrew Belch, Donna Reece, Meral Beksac, Eric Bleickardt, Valerie Poulart, Jennifer Sheng, Oumar Sy, Jessica Katz, Anil Singhal, Paul Richardson
The randomized phase III ELOQUENT-2 study (NCT01239797) evaluated the efficacy and safety of elotuzumab + lenalidomide/dexamethasone (ELd) versus lenalidomide/dexamethasone (Ld) in relapsed/refractory multiple myeloma. ELd reduced the risk of disease progression/death by 30% versus Ld (hazard ratio [HR] 0·70). Median time from diagnosis was 3·5 years. We present extended 3-year follow-up data. Endpoints included progression-free survival (PFS), overall response rate (ORR) and interim overall survival (OS)...
July 5, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28604269/elotuzumab-as-a-novel-anti-myeloma-immunotherapy
#7
Sabarinath Venniyil Radhakrishnan, Neelam Bhardwaj, Mary Steinbach, Janet Weidner, Tim Luetkens, Djordje Atanackovic
Treatment of multiple myeloma has undergone significant change in the last decade with the introduction of new immunomodulatory agents, proteasome inhibitors, and immunotherapeutic approaches. Elotuzumab is a humanized monoclonal antibody targeting CS1, which is a member of the SLAM (Signaling Lymphocyte Activation Molecule) family of proteins, expressed on the surface of myeloma plasma cells. Here we review the preclinical investigations that led to the development of elotuzumab and the clinical studies that resulted in its approval for the treatment of relapsed/refractory multiple myeloma...
August 3, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28601492/new-agents-in-multiple-myeloma-an%C3%A2-examination-of-safety-profiles
#8
REVIEW
Sara Bringhen, Edwin De Wit, Meletios-Athanassios Dimopoulos
Numerous treatments are available for relapsed and/or refractory multiple myeloma (MM), with safety profiles varying across drug classes and across agents within the same class. Thus, it is important to understand the toxicities of each antimyeloma agent when making treatment decisions. Neutropenia is commonly associated with lenalidomide and pomalidomide, and may be common with histone deacetylase (HDAC) inhibitors, but is relatively unusual with thalidomide, bortezomib, and carfilzomib. Infection was common in trials of lenalidomide and pomalidomide, and upper respiratory tract infection and pneumonia have been seen with carfilzomib...
May 10, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28561703/hematologic-malignancies-plasma-cell-disorders
#9
Madhav V Dhodapkar, Ivan Borrello, Adam D Cohen, Edward A Stadtmauer
Multiple myeloma (MM) is a plasma cell malignancy characterized by the growth of tumor cells in the bone marrow. Properties of the tumor microenvironment provide both potential tumor-promoting and tumor-restricting properties. Targeting underlying immune triggers for evolution of tumors as well as direct attack of malignant plasma cells is an emerging focus of therapy for MM. The monoclonal antibodies daratumumab and elotuzumab, which target the plasma cell surface proteins CD38 and SLAMF7/CS1, respectively, particularly when used in combination with immunomodulatory agents and proteasome inhibitors, have resulted in high response rates and improved survival for patients with relapsed and refractory MM...
2017: American Society of Clinical Oncology Educational Book
https://www.readbyqxmd.com/read/28556890/recent-progress-in-relapsed-multiple-myeloma-therapy-implications-for-treatment-decisions
#10
REVIEW
Philippe Moreau, Edwin de Wit
The availability of novel therapies for the treatment of multiple myeloma has had a dramatic impact on the depth of response that can be expected on initial treatment. Despite these advances, disease relapse remains inevitable in most patients and brings with it a different set of priorities for therapy. The most recent wave of novel agents may have a particular impact in the relapsed setting. In this review, we examine the evidence currently available from clinical trials for the use of novel agents, particularly in the formation of triplet therapy...
May 30, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28504554/how-is-patient-care-for-multiple-myeloma-advancing
#11
REVIEW
Sonja Genadieva Stavric, Francesca Bonello, Sara Bringhen, Mario Boccadoro, Alessandra Larocca
Treatment of multiple myeloma has undergone profound changes in the past years thanks to the increased understanding of the biology of the disease and the new treatment options. New drugs and effective approaches are currently available for the treatment of multiple myeloma, including immunomodulatory agents, proteasome inhibitors and autologous stem cell transplantation. Areas covered: We have described the recent updated criteria to start treatment in multiple myeloma and summarized clinical data from major studies including most recent agents...
June 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28454113/systematic-review-and-meta-analysis-of-the-efficacy-and-safety-of-novel-monoclonal-antibodies-for-treatment-of-relapsed-refractory-multiple-myeloma
#12
REVIEW
Tiantian Zhang, Sen Wang, Tengfei Lin, Jingmei Xie, Lina Zhao, Zhuoru Liang, Yangqiu Li, Jie Jiang
Although two newly launched monoclonal antibodies (mAbs), elotuzumab and daratumumab, performed well in patients with relapsed or relapsed/refractory multiple myeloma (RRMM), their efficacy and safety remain uncertain. We therefore performed a systematic review and meta-analysis of the most recent clinical trials that evaluated elotuzumab and/or daratumumab for the treatment of patients with RRMM. Our meta-analysis included 13 clinical trials with 2,402 patients participating. The overall response rate (ORR) was 57% (95% confidence interval [CI]: 38-76%), and the at least very good partial response rate (VGPR) was 32% (95% CI: 19-46%)...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28388244/which-therapies-will-move-to-the-front-line-for-multiple-myeloma
#13
REVIEW
María J Cejalvo, Javier de la Rubia
Despite substantial progress, multiple myeloma (MM) remains an incurable disease. Recently the availability of several novel drugs with different and innovative mechanisms of action (daratumumab, elotuzumab, carfilzomib, ixazomib, and panobinostat) has increased the therapeutic options but has also increased complexity in the management of patients with MM. Areas covered: The outstanding results observed in the relapsed setting with regimens including these new drugs has provided the investigators with several treatment options that are being tested also in patients with newly diagnosed MM...
May 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28356715/clinical-potential-of-slamf7-antibodies-focus-on-elotuzumab-in-multiple-myeloma
#14
REVIEW
Reed Friend, Manisha Bhutani, Peter M Voorhees, Saad Z Usmani
Elotuzumab is one of the first monoclonal antibodies to be approved for the treatment of multiple myeloma. It is a humanized immunoglobulin G kappa (IgGκ) antibody that targets signaling lymphocytic activation molecule family member 7 (SLAMF7), a surface marker that is highly expressed on normal and malignant plasma cells. This review summarizes the preclinical and clinical data that led to the approval of elotuzumab, along with a discussion on the ongoing and future clinical investigations.
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28325256/how-have-evolutions-in-strategies-for-the-treatment-of-relapsed-refractory-multiple-myeloma-translated-into-improved-outcomes-for-patients
#15
REVIEW
Pieter Sonneveld, Edwin De Wit, Philippe Moreau
Although multiple myeloma (MM) remains incurable, the introduction of novel agents has improved clinical outcomes dramatically over the past 15 years. Response rates have risen from ∼30% with single agents to up to 90% with combination therapies. The immunomodulatory drugs (IMiDs) thalidomide and lenalidomide, and the proteasome inhibitor bortezomib, form the foundations for treatment of relapsed and/or refractory MM (RRMM). Newer agents, such as the IMiD pomalidomide, the histone deacetylase inhibitor panobinostat and the proteasome inhibitors carfilzomib and ixazomib, as well as the monoclonal antibodies daratumumab and elotuzumab, have further improved overall response rates in these patients...
April 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28282035/randomized-phase-3-study-of-elotuzumab-for-relapsed-or-refractory-multiple-myeloma-eloquent-2-japanese-patient-subanalysis
#16
K Suzuki, K Sunami, K Ohashi, S Iida, T Mori, H Handa, K Matsue, M Miyoshi, E Bleickardt, M Matsumoto, M Taniwaki
No abstract text is available yet for this article.
March 10, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28259300/immunotherapy-for-the-treatment-of-multiple-myeloma
#17
REVIEW
Sung-Hoon Jung, Hyun-Ju Lee, Manh-Cuong Vo, Hyeoung-Joon Kim, Je-Jung Lee
Immunotherapy has recently emerged as a promising treatment for multiple myeloma (MM). There are now several monoclonal antibodies that target specific surface antigens on myeloma cells or the checkpoints of immune and myeloma cells. Elotuzumab (targeting SLAMF7), daratumumab (targeting CD38), and pembrolizumab (targeting PD-1) have shown clinical activity in clinical studies with relapsed/refractory MM. Dendritic cell vaccination is a safe strategy that has shown some efficacy in a subset of myeloma patients and may become a crucial part of MM treatment when combined with immunomodulatory drugs or immune check-point blockade...
March 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28254840/extracellular-matrix-and-the-myeloid-in-myeloma-compartment-balancing-tolerogenic-and-immunogenic-inflammation-in-the-myeloma-niche
#18
REVIEW
Fotis Asimakopoulos, Chelsea Hope, Michael G Johnson, Adam Pagenkopf, Kimberly Gromek, Bradley Nagel
The last 10-15 years have witnessed a revolution in treating multiple myeloma, an incurable cancer of Ab-producing plasma cells. Advances in myeloma therapy were ushered in by novel agents that remodel the myeloma immune microenvironment. The first generation of novel agents included immunomodulatory drugs (thalidomide analogs) and proteasome inhibitors that target crucial pathways that regulate immunity and inflammation, such as NF-κB. This paradigm continued with the recent regulatory approval of mAbs (elotuzumab, daratumumab) that impact both tumor cells and associated immune cells...
August 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28249893/fda-drug-approval-elotuzumab-in-combination-with-lenalidomide-and-dexamethasone-for-the-treatment-of-relapsed-or-refractory-multiple-myeloma
#19
Nicole J Gormley, Chia-Wen Ko, Albert Deisseroth, Lei Nie, Edvardas Kaminskas, Natasha Kormanik, Kirsten B Goldberg, Ann T Farrell, Richard Pazdur
On November 30, 2015, the U.S. Food and Drug Administration (FDA) approved elotuzumab (Empliciti, Bristol-Myers Squibb) in combination with lenalidomide and dexamethasone for treatment of patients with multiple myeloma who received one to three prior therapies. FDA approval was based primarily on results of a phase 3, randomized, open-label, multicenter trial, CA204004, that evaluated elotuzumab in combination with lenalidomide and dexamethasone (E-Ld), compared with lenalidomide and dexamethasone (Ld) alone, in patients with relapsed or refractory multiple myeloma...
March 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28213943/a-phase-2-safety-study-of-accelerated-elotuzumab-infusion-over-less-than-1-h-in-combination-with-lenalidomide-and-dexamethasone-in-patients-with-multiple-myeloma
#20
James Berenson, Robert Manges, Suprith Badarinath, Alan Cartmell, Kristi McIntyre, Roger Lyons, Wael Harb, Hesham Mohamed, Ali Nourbakhsh, Robert Rifkin
Elotuzumab, an immunostimulatory SLAMF7-targeting monoclonal antibody, induces myeloma cell death with minimal effects on normal tissue. In a previous phase 3 study in patients with relapsed/refractory multiple myeloma (RRMM), elotuzumab (10 mg/kg, ∼3-h infusion), combined with lenalidomide and dexamethasone, demonstrated durable efficacy and acceptable safety; 10% (33/321) of patients had infusion reactions (IRs; Grade 1/2: 29; Grade 3: 4). This phase 2 study (NCT02159365) investigated an accelerated infusion schedule in 70 patients with newly diagnosed multiple myeloma or RRMM...
May 2017: American Journal of Hematology
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