Focus on monoclonal antibodies targeting B‐cell maturation antigen (BCMA) in multiple myeloma: update 2020

2020 ◽  
Author(s):  
Ivo Demel ◽  
Julio Rodriguez Bago ◽  
Roman Hajek ◽  
Tomas Jelinek
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibodies ◽  
B Cell ◽  
Cell Maturation ◽  
B Cell Maturation ◽  
B Cell Maturation Antigen

scholarly journals B-Cell Maturation Antigen (BCMA) As a Target for New Drug Development in Relapsed and/or Refractory Multiple Myeloma

2020 ◽  
Author(s):  
Hanley N. Abramson
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibodies ◽  
T Cell ◽  
B Cell ◽  
Plasma Cells ◽  
Cell Types ◽  
Cell Maturation ◽  
New Drug ◽  
B Cell Maturation ◽  
B Cell Maturation Antigen

During the past two decades there has been a major shift in the choice of agents to treat multiple myeloma, whether newly diagnosed or in the relapsed/refractory stage. The introduction of new drug classes, such as proteasome inhibitors, immunomodulators, and anti-CD38 and anti-SLAMF7 monoclonal antibodies, coupled with autologous stem cell transplantation, have approximately doubled the disease’s five-year survival rate. However, this positive news is tempered by the realization that these measures are not curative and patients eventually relapse and/or become resistant to the drug’s effects. Thus, there is a need to discover newer myeloma-driving molecular markers and develop innovative drugs designed to precisely regulate the actions of such putative targets. B cell maturation antigen (BCMA), which is found almost exclusively on the surfaces of malignant plasma cells to the exclusion of other cell types, including their normal counterparts, has emerged as a specific target of interest in this regard. Immunotherapeutic agents have been at the forefront of research designed to block BCMA activity. These agents encompass monoclonal antibodies, such as the drug conjugate belantamab mafodotin; bispecific T-cell engager strategies exemplified by AMG 420; and chimeric antigen receptor (CAR) T-cell therapeutics that include idecabtagene vicleucel (bb2121) and JNJ-68284528.

scholarly journals B-Cell Maturation Antigen (BCMA) as a Target for New Drug Development in Relapsed and/or Refractory Multiple Myeloma

2020 ◽  
Vol 21 (15) ◽  
pp. 5192 ◽  
Author(s):  
Hanley N. Abramson
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibodies ◽  
T Cell ◽  
B Cell ◽  
Plasma Cells ◽  
Cell Types ◽  
Cell Maturation ◽  
New Drug ◽  
B Cell Maturation ◽  
B Cell Maturation Antigen

During the past two decades there has been a major shift in the choice of agents to treat multiple myeloma, whether newly diagnosed or in the relapsed/refractory stage. The introduction of new drug classes, such as proteasome inhibitors, immunomodulators, and anti-CD38 and anti-SLAMF7 monoclonal antibodies, coupled with autologous stem cell transplantation, has approximately doubled the disease’s five-year survival rate. However, this positive news is tempered by the realization that these measures are not curative and patients eventually relapse and/or become resistant to the drug’s effects. Thus, there is a need to discover newer myeloma-driving molecular markers and develop innovative drugs designed to precisely regulate the actions of such putative targets. B cell maturation antigen (BCMA), which is found almost exclusively on the surfaces of malignant plasma cells to the exclusion of other cell types, including their normal counterparts, has emerged as a specific target of interest in this regard. Immunotherapeutic agents have been at the forefront of research designed to block BCMA activity. These agents encompass monoclonal antibodies, such as the drug conjugate belantamab mafodotin; bispecific T-cell engager strategies exemplified by AMG 420; and chimeric antigen receptor (CAR) T-cell therapeutics that include idecabtagene vicleucel (bb2121) and JNJ-68284528.

scholarly journals B-cell maturation antigen (BCMA) in multiple myeloma: the new frontier of targeted therapies

2021 ◽  
Vol 12 ◽  
pp. 204062072198958
Author(s):  
Larysa Sanchez ◽  
Alexandra Dardac ◽  
Deepu Madduri ◽  
Shambavi Richard ◽  
Joshua Richter
Keyword(s):  
Multiple Myeloma ◽  
T Cell ◽  
B Cell ◽  
Targeted Therapies ◽  
Safety Data ◽  
Cell Maturation ◽  
Treatment Modalities ◽  
Cell Therapies ◽  
B Cell Maturation ◽  
B Cell Maturation Antigen

Outcomes of patients with multiple myeloma (MM) who become refractory to standard therapies are particularly poor and novel agents are greatly needed to improve outcomes in such patients. B-cell maturation antigen (BCMA) has become an important therapeutic target in MM with three modalities of treatment in development including antibody–drug conjugates (ADCs), bispecific T-cell engagers (BITEs), and chimeric antigen receptor (CAR) T-cell therapies. Early clinical trials of anti-BCMA immunotherapeutics have demonstrated extremely promising results in heavily pretreated patients with relapsed/refractory MM (RRMM). Recently, belantamab mafodotin was the first anti-BCMA therapy to obtain approval in relapsed/refractory MM. This review summarizes the most updated efficacy and safety data from clinical studies of BCMA-targeted therapies with a focus on ADCs and BITEs. Additionally, important differences among the BCMA-targeted treatment modalities and their clinical implications are discussed.

scholarly journals B-cell Maturation Antigen Is a Promising Target for Adoptive T-cell Therapy of Multiple Myeloma

2013 ◽  
Vol 19 (8) ◽  
pp. 2048-2060 ◽  
Author(s):  
Robert O. Carpenter ◽  
Moses O. Evbuomwan ◽  
Stefania Pittaluga ◽  
Jeremy J. Rose ◽  
Mark Raffeld ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
Adoptive T Cell Therapy ◽  
Cell Maturation ◽  
T Cell Therapy ◽  
B Cell Maturation ◽  
Promising Target ◽  
B Cell Maturation Antigen

scholarly journals Evaluation of B cell maturation antigen as a target for antibody drug conjugate mediated cytotoxicity in multiple myeloma

2016 ◽  
Vol 174 (6) ◽  
pp. 911-922 ◽  
Author(s):  
Lydia Lee ◽  
Danton Bounds ◽  
Jennifer Paterson ◽  
Gaelle Herledan ◽  
Katherine Sully ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
B Cell ◽  
Cell Maturation ◽  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
B Cell Maturation ◽  
B Cell Maturation Antigen ◽  
Antibody Drug

scholarly journals Chimeric Antigen Receptor-Modified T Cell Therapy in Multiple Myeloma: Beyond B Cell Maturation Antigen

2019 ◽  
Vol 10 ◽  
Author(s):  
Marijke Timmers ◽  
Gils Roex ◽  
Yuedi Wang ◽  
Diana Campillo-Davo ◽  
Viggo F. I. Van Tendeloo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Cell Maturation ◽  
T Cell Therapy ◽  
B Cell Maturation ◽  
B Cell Maturation Antigen

scholarly journals T Cells Genetically Modified to Express an Anti–B-Cell Maturation Antigen Chimeric Antigen Receptor Cause Remissions of Poor-Prognosis Relapsed Multiple Myeloma

2018 ◽  
Vol 36 (22) ◽  
pp. 2267-2280 ◽  
Author(s):  
Jennifer N. Brudno ◽  
Irina Maric ◽  
Steven D. Hartman ◽  
Jeremy J. Rose ◽  
Michael Wang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
T Cells ◽  
Partial Response ◽  
B Cell ◽  
Residual Disease ◽  
Cell Maturation ◽  
B Cell Maturation ◽  
Minimal Residual ◽  
B Cell Maturation Antigen

Purpose Therapies with novel mechanisms of action are needed for multiple myeloma (MM). T cells can be genetically modified to express chimeric antigen receptors (CARs), which are artificial proteins that target T cells to antigens. B-cell maturation antigen (BCMA) is expressed by normal and malignant plasma cells but not normal essential cells. We conducted the first-in-humans clinical trial, to our knowledge, of T cells expressing a CAR targeting BCMA (CAR-BCMA). Patients and Methods Sixteen patients received 9 × 106 CAR-BCMA T cells/kg at the highest dose level of the trial; we are reporting results of these 16 patients. The patients had a median of 9.5 prior lines of MM therapy. Sixty-three percent of patients had MM refractory to the last treatment regimen before protocol enrollment. T cells were transduced with a γ-retroviral vector encoding CAR-BCMA. Patients received CAR-BCMA T cells after a conditioning chemotherapy regimen of cyclophosphamide and fludarabine. Results The overall response rate was 81%, with 63% very good partial response or complete response. Median event-free survival was 31 weeks. Responses included eradication of extensive bone marrow myeloma and resolution of soft-tissue plasmacytomas. All 11 patients who obtained an anti-MM response of partial response or better and had MM evaluable for minimal residual disease obtained bone marrow minimal residual disease–negative status. High peak blood CAR+ cell levels were associated with anti-MM responses. Cytokine-release syndrome toxicities were severe in some cases but were reversible. Blood CAR-BCMA T cells were predominantly highly differentiated CD8+ T cells 6 to 9 days after infusion. BCMA antigen loss from MM was observed. Conclusion CAR-BCMA T cells had substantial activity against heavily treated relapsed/refractory MM. Our results should encourage additional development of CAR T-cell therapies for MM.

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