B-cell maturation antigen (BCMA) in multiple myeloma: rationale for targeting and current therapeutic approaches
Open accessAbstract
Despite considerable advances in the treatment of multiple myeloma (MM) in the last decade, a substantial proportion of patients do not respond to current therapies or have a short duration of response. Furthermore, these treatments can have notable morbidity and are not uniformly tolerated in all patients. As there is no cure for MM, patients eventually become resistant to therapies, leading to development of relapsed/refractory MM. Therefore, an unmet need exists for MM treatments with novel mechanisms of action that can provide durable responses, evade resistance to prior therapies, and/or are better tolerated. B-cell maturation antigen (BCMA) is preferentially expressed by mature B lymphocytes, and its overexpression and activation are associated with MM in preclinical models and humans, supporting its potential utility as a therapeutic target for MM. Moreover, the use of BCMA as a biomarker for MM is supported by its prognostic value, correlation with clinical status, and its ability to be used in traditionally difficult-to-monitor patient populations. Here, we review three common treatment modalities used to target BCMA in the treatment of MM: bispecific antibody constructs, antibody–drug conjugates, and chimeric antigen receptor (CAR)-modified T-cell therapy. We provide an overview of preliminary clinical data from trials using these therapies, including the BiTE® (bispecific T-cell engager) immuno-oncology therapy AMG 420, the antibody–drug conjugate GSK2857916, and several CAR T-cell therapeutic agents including bb2121, NIH CAR-BCMA, and LCAR-B38M. Notable antimyeloma activity and high minimal residual disease negativity rates have been observed with several of these treatments. These clinical data outline the potential for BCMA-targeted therapies to improve the treatment landscape for MM. Importantly, clinical results to date suggest that these therapies may hold promise for deep and durable responses and support further investigation in earlier lines of treatment, including newly diagnosed MM.
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Elranatamab is a humanized B-cell maturation antigen (BCMA)-CD3 bispecific antibody that targets both BCMA and CD3.
“Elranatamab is a humanized B-cell maturation antigen (BCMA)-CD3 bispecific antibody.”
From Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results (2023) · cites this paper as [3]
The Bispecific antibody constructs section describes PF-06863135 (PF-3135) as a humanized antibody with anti-BCMA and anti-CD3 arms. Our copy does not name elranatamab or identify it as PF-06863135, so it does not establish that the description applies to elranatamab. (LLM, conf=0.78)
Experimental — accuracy not yet measuredCAR-T therapy requires that patients have access to specialized care centers and can wait the minimum 4-week period for production, which can result in attrition rates of approximately 10 to 15%.
“CAR-T therapy requires that patients have access to specialized care centers and can wait the minimum 4-week period for production, which can result in attrition rates of approximately 10 to 15%,6-8”
From Teclistamab in Relapsed or Refractory Multiple Myeloma (2022) · cites this paper as [7]
The Discussion and future perspectives section (page unavailable) says CAR T-cell treatment involves a specialized center and that manufacturing takes several days to weeks, during which disease may progress. It does not establish a minimum four-week production period or an attrition rate of approximately 10–15%. (LLM, conf=0.88)
Experimental — accuracy not yet measuredBCMA is highly expressed on malignant plasma cells, making it an ideal target for treatment of multiple myeloma.
“B-cell maturation antigen (BCMA), a member of the tumor necrosis factor receptor superfamily, is highly expressed on malignant plasma cells, making it an ideal target for the treatment of multiple myeloma3.”
From Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results (2023) · cites this paper as [3]
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Chimeric Antigen Receptor T-Cell Therapy
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Anti-BCMA immunotoxins produce durable complete remissions in two mouse myeloma models
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BCMA CAR T-cell therapy arrives for multiple myeloma: a reality
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Teclistamab in Relapsed or Refractory Multiple Myeloma
Moreau, P., Garfall, A. L., van de Donk, N. W. C. J., Nahi, H., San-Miguel, J. F., Oriol, A., Nooka, A. K., Martin, T., Rosinol, L., Chari, A., et al. (2022) · New England Journal of Medicine · doi:10.1056/nejmoa2203478 · Cited by 1,269 · see citing works
Self-citationElranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results
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GPRC5D as a novel target for the treatment of multiple myeloma: a narrative review
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Self-citationRisk of infections with B-cell maturation antigen-directed immunotherapy in multiple myeloma
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Clinical management of patients with relapsed/refractory multiple myeloma treated with talquetamab
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Self-citationLi, G.-Q., Wang, Y.-K., Zhou, H., Jin, L.-G., Wang, C.-Y., Albahde, M., Wu, Y., Li, H.-Y., Zhang, W.-K., Li, B.-H., et al. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.630355 · Cited by 24 · see citing works
- Authors
- Shah, N., Chari, A., Scott, E., Mezzi, K., & Usmani, S. Z.
- Affiliations
- University of California, San Francisco (US)
- Mount Sinai Hospital (US)
- GlaxoSmithKline (United States) (US)
- Amgen (United States) (US)
- Corresponding author
- Shah, Nina
- Venue
- Leukemia
- Published
- 2020-02-13
- Volume
- 34
- Issue
- 4
- Pages
- 985-1005
- ISSN
- 0887-6924 (ISSN-L)
- 1476-5551
- PMC
- PMC7214244
- OpenAlex
- W3006655689
- Cited by
- 490
- References
- 109
- Citations by year
- 2026: 52 · 2025: 74 · 2024: 90 · 2023: 79 · 2022: 84 · 2021: 70 · 2020: 40 · 2019: 1
- FWCI
- 10.71
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Leukemia (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- Amgen
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Keywords
- BCMA, multiple myeloma, BCMA-targeted therapy, bispecific T-cell engagers, antibody-drug conjugates, CAR T-cell therapy, relapsed/refractory multiple myeloma, minimal residual disease, prognostic factors, treatment resistance
- MeSH terms
- Antineoplastic Agents, Immunological, Antineoplastic Combined Chemotherapy Protocols, B-Lymphocytes, Clinical Trials as Topic, Humans, Multiple Myeloma, Recurrence, Biomarkers, Tumor, Gene Expression, Immunotherapy, Adoptive, Treatment Outcome, Antibodies, Bispecific, Immunoconjugates, Drug Resistance, Neoplasm, B-Cell Maturation Antigen, Molecular Targeted Therapy, Antibodies, Monoclonal, Humanized
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