BCMAdirected

BCMAdirected refers to therapies that target B-cell maturation antigen (BCMA), a cell-surface receptor encoded by the TNFRSF17 gene. BCMA is highly expressed on mature B cells and, importantly, on malignant plasma cells in multiple myeloma, making it a strategic target for anti-myeloma treatments. BCMA-directed approaches aim to eliminat e BCMA-expressing cells or to recruit immune effector mechanisms to attack them.

The primary modalities of BCMAdirected therapy include chimeric antigen receptor (CAR) T cells, bispecific antibodies that redirect T cells to BCMA, and antibody-drug conjugates. CAR T-cell therapies involve collecting a patient’s T cells, engineering them to recognize BCMA, and reinfusing them to attack myeloma cells. Notable products include BCMA-directed CAR T cells such as idecabtagene vicleucel and ciltacabtagene autoleucel, approved for relapsed or refractory multiple myeloma after multiple prior therapies in various jurisdictions. Bispecific antibodies, such as teclistamab, bind BCMA on myeloma cells and CD3 on T cells to mediate T-cell–driven cytotoxicity. Antibody-drug conjugates deliver cytotoxic payloads directly to BCMA-expressing cells; belantamab mafodotin is an example, though its clinical use has undergone regulatory reevaluation in some regions.

Clinical use typically centers on relapsed or refractory multiple myeloma, often after multiple prior lines of therapy. Common adverse effects across BCMAdirected therapies include cytokine-release syndrome and neurotoxicity for CAR T-cell and bispecific approaches, along with hematologic toxicities and, in some BCMA-directed ADCs, ocular toxicity or keratopathy.

Ongoing research investigates optimization of sequencing, combination regimens, resistance mechanisms, and management of safety concerns to broaden the accessibility and durability of BCMA-directed treatments.