The approval of the first two monoclonal antibodies in the treatment of patients with relapsed and refractory multiple myeloma was a watershed moment for the multiple myeloma community in 2015. Despite early setbacks, monoclonal antibodies targeting CD38 (daratumumab) and signalling lymphocytic activation molecule F7 (SLAMF7) (elotuzumab) for patients with multiple myeloma became available in the same year for patients with multiple myeloma. Phase 3 clinical trials of combination treatments containing daratumumab or elotuzumab, in particular, have shown efficacy as well as a low safety profile. These monoclonal antibodies for multiple myeloma can kill target cells through antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, antibody-dependent phagocytosis, and direct signalling cascade blocking. Furthermore, their immunomodulatory activities may inhibit the immunosuppressive bone marrow microenvironment while also restoring immune effector cell activity. We focus on monoclonal antibodies that have shown clinical efficacy or have potential preclinical anti-multiple myeloma actions that warrant further clinical development in our study. We review the mechanisms underlying these monoclonal antibodies' anti-myeloma activities in vitro and in vivo, as well as pertinent preclinical and clinical findings. Monoclonal antibody-based immunotherapies have already changed the therapy landscape for multiple myeloma and will continue to do so.
