Monoclonal Antibodies and Antibody-Drug Conjugates: Expanding the Therapeutic Arsenal in Multiple Myeloma.

Abstract

Monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs) have significantly expanded the therapeutic landscape of multiple myeloma (MM), contributing to deeper and more durable responses and meaningful survival benefits across the continuum of the disease. CD38-targeting mAbs are now integral to frontline regimens, while ADCs introduce a complementary strategy by enabling targeted delivery of cytotoxic payloads, most notably through B-cell maturation antigen (BCMA). However, the clinical integration of these agents has revealed new resistant mechanisms, including antigen loss, immune exhaustion, and the emergence of cross-resistance across BCMA-directed therapies. Furthermore, challenges in the sequencing of treatments have emerged, as novel immunotherapies have also become available in the early relapse setting. This contemporary review examines the evolving role of mAbs and ADCs in MM, addressing both current status and directions for future research in the field.