Relapsed/Refractory Multiple Myeloma: Expanding Beyond BCMA With GPRC5D Targeting

Dr. Ajai Chari and Dr. Rahul Banerjee discuss the growing need for therapeutic targets beyond BCMA in relapsed/refractory multiple myeloma (RRMM) and examine the rationale for GPRC5D-directed therapies. While acknowledging the significant advances achieved with BCMA-targeted treatments, the faculty highlight limitations including treatment resistance, patient selection considerations, and the risk of infections associated with broad BCMA expression. Dr. Chari emphasizes the importance of identifying additional targets to further improve long-term outcomes and move closer to the goal of achieving durable disease control and potential cure. The discussion explores the unique biology of GPRC5D, its restricted expression pattern on malignant plasma cells, and how this differentiates it from BCMA. Dr. Banerjee reviews the clinical development of talquetamab and the potential advantages of targeting distinct antigens, particularly in patients previously exposed to BCMA-directed therapies. The faculty also consider how emerging targets and combination strategies may help overcome resistance mechanisms and shape the future treatment landscape for patients with RRMM.