Positioning GPRC5D-Directed Therapy in Relapsed/Refractory Multiple Myeloma

Dr. Hans Lee and Dr. Prashant Kapoor discuss the potential role of talquetamab-based therapy in the evolving treatment sequence for relapsed/refractory multiple myeloma. The panel reviews TAL3 data evaluating talquetamab in combination with daratumumab with or without pomalidomide compared with daratumumab, pomalidomide, and dexamethasone, including improvements in progression-free and overall survival. Dr. Kapoor considers how talquetamab-based therapy may provide an alternative to BCMA-directed therapies, particularly for patients at greater risk of infectious complications. He discusses the similar outcomes observed with talquetamab plus daratumumab compared with the triplet containing pomalidomide, while noting the potential for additional toxicity with the third agent. The discussion also addresses the distinct toxicity profile associated with GPRC5D targeting, including skin and nail toxicities and emerging concerns regarding ataxia or disequilibrium. The experts highlight the importance of recognizing and managing these unique adverse effects as GPRC5D-directed therapies become increasingly integrated into treatment sequencing.