B-cell maturation antigen (BCMA) and G protein-coupled receptor class C group 5 member D (GPRC5D) (BCMA/GPRC5D)

B-cell maturation antigen (BCMA) and G protein-coupled receptor class C group 5 member D (GPRC5D) are two of the most validated surface antigens for the treatment of multiple myeloma [1, 8]. BCMA is a member of the tumor necrosis factor receptor superfamily (TNFRSF17) that is essential for the survival of long-lived plasma cells and is highly expressed on malignant plasma cells [3, 7]. GPRC5D is an orphan G protein-coupled receptor with a highly restricted expression pattern, found primarily on plasma cells and in hard keratinized tissues such as hair follicles [11, 13]. Dual targeting of these antigens, either through combination therapy with bispecific antibodies or via multi-specific chimeric antigen receptor (CAR) T-cell therapies, is a strategic approach designed to overcome antigen escape and improve therapeutic durability [5, 10, 22]. This dual-targeting strategy has shown significant clinical activity, particularly in patients with relapsed or refractory disease and those with aggressive extramedullary involvement [2, 4, 15, 20]. Notable safety concerns include cytokine release syndrome (CRS), neurotoxicity, and target-specific toxicities such as dysgeusia and skin/nail changes associated with GPRC5D inhibition [19, 21].

Other names

TNFRSF17CD269BCMB-cell maturation factor receptorGPRC5DG protein-coupled receptor class C group 5 member D

Drugs targeting BCMA and GPRC5D primarily utilize T-cell redirection (bispecific antibodies), chimeric antigen receptor (CAR) T-cell therapy, or antibody-drug conjugates (ADCs) to induce targeted lysis of malignant plasma cells [2, 5, 14].