GPRC5D-targeting bispecific and trispecific antibodies in multiple myeloma: Current evidence and emerging strategies.

Abstract

G-protein-coupled receptor class C group 5 member D (GPRC5D) has emerged as a crucial immunotherapy target in relapsed/refractory multiple myeloma. Although the T-cell-engaging bispecific antibody talquetamab is currently the only approved anti-GPRC5D therapy, numerous promising agents are undergoing clinical evaluation. While anti-GPRC5D chimeric antigen receptor T cells show potential, this review focuses specifically on T-cell-engaging bispecific and trispecific antibodies. We highlight how GPRC5D differs clinically from B-cell maturation antigen, explore mechanisms of resistance, discuss novel therapeutic strategies including combination regimens and talquetamab as bridging therapy to chimeric antigen receptor T cells, and review key investigational T-cell engagers currently in development.