Multiple myeloma is a remitting-relapsing disease that requires multiple lines of treatment. Despite the availability of proteasome inhibitors, immunomodulatory agents, and monoclonal antibodies, response rates and prognosis diminish with each subsequent therapy. In triple- and quad-refractory myeloma, median survival is only about 9 months, and less than 6 months in penta-refractory disease.
B-cell maturation antigen (BCMA) is an effective anti-myeloma target due to its specific surface expression on malignant plasma cells and non-expression in normal tissue and hematopoietic cells.
BCMA can be targeted with CAR T-cell strategies that involve genetically modifying a patient’s own T cells to attack the BCMA target on myeloma cells. More recently, bispecific antibodies have been developed to bind the BCMA target on myeloma cells to T-cell CD3 receptors, eliciting a cytotoxic effect.
Two BCMA CAR T-cell therapies, idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), are approved for the treatment of adults who have had ≥4 lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. More recently, the first bispecific antibody, teclistamab, was granted accelerated approval with the same indication. Additional bispecific antibodies with strong clinical trial data include linvoseltamab and elranatamab.
BCMA CAR T-cell therapies require a single treatment but have a long manufacturing time that may not be ideal for patients with rapidly progressing disease. They also require stringent evaluation of organ function, cardiac and neurologic clearance, and an extended stay at a specialized center. In contrast, BCMA bispecific antibodies are available off-the-shelf for immediate use and require less stringent evaluation. Hospitalization is limited to the step-up dosing schedule that mitigates the risk for cytokine release syndrome (CRS).
CRS and immune effector cell-associated neurotoxicity syndrome (ICANS) are associated with both treatment options but occur less frequently with BCMA-targeting bispecific antibodies. Infections are common with both approaches and prophylaxis is recommended.
The decision between BCMA CAR-T therapy and BCMA bispecific antibodies for the treatment of multiple myeloma is complex and depends on several factors, including overall patient health, disease characteristics, prior treatments, and potential side effects. Practical considerations may also play a role in the decision-making process.
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Exploiting BCMA in the Treatment of Multiple Myeloma: How Could Bispecific Antibodies and T-Cell Engagement Impact Relapsed/Refractory Disease? Proceedings from a Clinical Olympics℠
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