Relapsed/Refractory Multiple Myeloma: Clinical Development and Early Experience With Talquetamab

Dr. Ajai Chari and Dr. Rahul Banerjee review the clinical development of talquetamab in relapsed/refractory multiple myeloma (RRMM), focusing on key findings from the MonumenTAL-1 study and the evolution of GPRC5D-directed therapy. Dr. Chari discusses the rationale for targeting GPRC5D, highlighting its distinct biology and lack of soluble antigen expression compared with BCMA. The faculty examine the activity observed in heavily pretreated patient populations, including individuals previously exposed to T-cell–redirecting therapies, and discuss how these findings helped establish talquetamab as a promising therapeutic option. The conversation also explores the unique safety profile associated with GPRC5D targeting, including oral toxicities, taste changes, skin and nail effects, and weight loss, while noting the comparatively lower incidence of infectious complications observed in clinical studies. Dr. Chari and Dr. Banerjee further discuss lessons learned regarding dosing optimization, treatment interval modifications, and T-cell fitness, highlighting how these observations informed subsequent clinical development and the design of later-phase studies evaluating talquetamab in RRMM.