Sequencing Therapy After BCMA-Directed CAR T and Bispecific Antibodies in Multiple Myeloma

Dr. Hans Lee, Dr. Muhamed Baljevic, and Dr. Prashant Kapoor discuss treatment strategies for patients with multiple myeloma who relapse following BCMA-directed CAR T-cell therapy or bispecific antibodies. Dr. Baljevic highlights the possibility of sequencing BCMA-directed therapies after prior BCMA exposure, particularly when the initial response was deep and durable, while noting that switching targets may be preferable after a short-lived or suboptimal response. The panel considers potential mechanisms of resistance, including changes in BCMA expression, epitope mutations, antigen shedding, and downregulation, and how these factors may influence subsequent treatment selection. The discussion also explores emerging sequencing strategies involving alternative targets such as GPRC5D, combinations with partner agents including immunomodulatory drugs and CELMoDs, and the potential role of trispecific therapies. Finally, the experts emphasize the importance of T-cell fitness and immune recovery when sequencing T-cell redirecting therapies, including the potential value of treatment spacing or intervening approaches to preserve T-cell function and optimize subsequent responses.