The identification and targeting of B cell maturation antigen (BCMA) through immunotherapeutic strategies such as antibody-drug conjugates (ADC), chimeric antigen receptor T-cells (CAR T-cells), and T-cell engagers (TCE) have revolutionized the care of patients with multiple myeloma (MM). These treatment modalities have improved survival outcomes of relapsed and/or refractory (R/R) MM patients compared to previously established strategies and are moving into earlier lines of therapy (LOT). Despite their efficacy, the majority of patients eventually relapse, necessitating additional therapeutic targets for salvage. G-protein-coupled receptor class 5 member D (GPRC5D), Fc receptor-homolog 5 (FcRH5), and SLAMF7 are some examples of novel targets in development. This expanding armamentarium of immunotherapeutic agents will be crucial to address the unmet need for relapses following BCMA-targeting therapies, particularly antigen-negative relapses. The utilization of sequential T-cell redirective therapies including agents targeting different tumor-associated antigens and combination therapies appears feasible paves the way for effective chemotherapy-free regimes. Deliberate consideration of treatment timing, preserving T-cell health, overcoming antigenic loss, and comprehension of the complex tumor microenvironment would be key to maximizing therapeutic benefits and minimizing adverse effects. This review summarizes novel targets in development for myeloma beyond BCMA, presenting pivotal safety and efficacy data derived from clinical trials where available and the considerations vital for navigating this expanding landscape of immunotherapeutic options.
Review Article|
June 12, 2024
Beyond BCMA: newer immune targets in myeloma
Melinda SY Tan,
Melinda SY Tan
Singapore General Hospital, Singapore, Singapore
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Yunxin Chen,
Yunxin Chen
Singapore General Hospital, Singapore, Singapore
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Eric L Smith
Dana-Farber Cancer Institute, Boston, Massachusetts, United States
* Corresponding Author; email: ericl_smith@dfci.harvard.edu
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Blood Adv bloodadvances.2023010856.
Article history
Submitted:
December 12, 2023
Revision Received:
May 29, 2024
Accepted:
May 31, 2024
Citation
Melinda SY Tan, Yunxin Chen, Eric L Smith; Beyond BCMA: newer immune targets in myeloma. Blood Adv 2024; bloodadvances.2023010856. doi: https://doi.org/10.1182/bloodadvances.2023010856
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