Talquetamab for the treatment of relapsed/refractory multiple myeloma: a review of efficacy, safety, and real-world evidence.

INTRODUCTION: Talquetamab is a GPRC5DxCD3 T-cell-engaging bispecific antibody approved for the treatment of relapsed/refractory multiple myeloma. GPRC5D represents a novel and emerging target in antimyeloma therapy, and there is substantial drug development for new therapies targeting this antigen.

AREAS COVERED: Herein, we review the efficacy, safety, and future development directions of talquetamab, including emerging talquetamab-based combination regimens and ongoing clinical trials. We will also review the growing landscape of GPRC5D-targeting immunotherapies in development for multiple myeloma, including CAR-T and trispecific antibodies.

EXPERT OPINION: Talquetamab, a GPRC5D-targeting bispecific antibody, was FDA-approved in 2023 for relapsed/refractory multiple myeloma after 4 or more prior lines of therapy. In contrast to the historic overall response rate (ORR) of 29.5%, talquetamab monotherapy achieved a promising ORR of ~70% in a triple-class-exposed population. Real-world evidence supports talquetamab as a bridging therapy to CAR-T. Notable adverse drug reactions include CRS, dysgeusia, nail/skin toxicities, and infections, which are often manageable but can be persistent. Sequencing studies suggest talquetamab retains efficacy before or after BCMA-directed therapies without diminishing effectiveness. Potential future directions for talquetamab include combination regimens with other antimyeloma therapies. Additional GPRC5D-directed therapies are also under development, including trispecific antibodies and CAR-T.