GPRC5D-Directed Bispecific Antibodies in Relapsed/Refractory Multiple Myeloma

In this segment, Dr. Peter Voorhees discusses the MonumenTAL-3 study evaluating the GPRC5D-directed bispecific antibody talquetamab in earlier-line relapsed/refractory multiple myeloma. He reviews the study design, including the two experimental arms evaluating talquetamab alone and in combination with daratumumab versus standard-of-care daratumumab, pomalidomide, and dexamethasone. Dr. Voorhees notes that patients had received at least 1 prior line of therapy and, similar to MajesTEC-3, could have prior CD38 antibody exposure but could not have CD38-refractory disease. He highlights higher overall response rates, complete response rates, and MRD negativity with the experimental regimens, along with improvements in progression-free survival and an overall survival signal. The discussion then contrasts the toxicity profiles of GPRC5D- and BCMA-directed therapies. Dr. Voorhees describes the relatively preferential expression of GPRC5D on plasma cells and discusses the distinct toxicities associated with talquetamab, including skin and oral effects, taste disturbance, and ataxia or balance disorders. He emphasizes counseling patients about these effects, monitoring closely during treatment, and recognizing that taste-related symptoms may improve over time.