A review of the clinical efficacy of monoclonal antibody (mAb)-based therapies for relapsed/refractory multiple myeloma (RRMM)

INTRODUCTION: Monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs) are among the backbones of treatment for relapsed/refractory multiple myeloma (RRMM). Beyond current standard-of-care regimens, the roles of mAbs/ADCs are evolving associated with advances in first-line therapy, emerging data on additional regimens, and developments with immunotherapies and other novel agents. AREAS COVERED: We review mechanisms of action, efficacy, real-world effectiveness, and key aspects of the safety profiles of daratumumab, isatuximab, elotuzumab, and belantamab mafodotin in RRMM. We consider efficacy in patient subgroups and the challenges of treatment sequencing and highlight new antigen targets and mAb/ADC therapies under investigation. We searched the published literature with PubMed and congress abstracts using drug names or classes and 'myeloma.' EXPERT OPINION: The widespread use of daratumumab and isatuximab in first-line therapy and evolving roles of CAR T-cell therapies and bispecific antibodies are reshaping RRMM treatment. mAb/ADC-based regimens remain key options in this setting, offering practical, effective, and tolerable approaches for real-world practice. Ongoing research will inform individualized treatment choices and rational sequencing of therapies, with a need for immune-based biomarkers and biologic profiling to enable optimal, integrated use of mAbs, ADCs, CAR T-cell therapies, and bispecific antibodies to further improve outcomes for patients with RRMM.