BCMAtargeted

BCMA-targeted therapies are treatments directed at the B-cell maturation antigen (BCMA), a cell-surface protein highly expressed on malignant plasma cells in multiple myeloma. BCMA belongs to the TNF receptor family and has limited expression in most normal tissues, making it a favorable target for selective anti-myeloma interventions.

Therapeutic modalities include: CAR-T cell therapy, where a patient’s T cells are engineered to recognize BCMA; antibody-drug conjugates, which deliver cytotoxic payloads to BCMA-expressing cells; and bispecific antibodies that recruit T cells to kill BCMA-positive cells. Notable examples include autologous BCMA-directed CAR-T constructs, BCMA-targeted antibody-drug conjugates such as belantamab mafodotin, and a range of bispecific formats under development.

Clinical activity has been demonstrated in relapsed or refractory multiple myeloma, with response and durability varying by product and prior lines of therapy. Safety concerns include cytokine release syndrome and neurotoxicity with CAR-T therapy; ocular toxicity and cytopenias with antibody-drug conjugates; and infection risk with several BCMA-directed agents. Resistance mechanisms, such as BCMA downregulation, are under investigation. Manufacturing complexity and access remain practical challenges.

Future directions focus on combination regimens, next-generation BCMA constructs, and strategies to mitigate adverse effects and resistance. The BCMA-targeted approach remains a central area in myeloma therapy development, with ongoing trials expanding indications and optimizing sequencing of BCMA-directed treatments.