Antibody–Drug Conjugates for Multiple Myeloma: Just the Beginning, or the Beginning of the End?

Abstract

Multiple myeloma is a malignancy of immunoglobulin-secreting plasma cells that is now often treated in the newly diagnosed and relapsed and/or refractory settings with monoclonal antibodies targeting lineage-specific markers used either alone or in rationally designed combination regimens. Among these are the anti-CD38 antibodies daratumumab and isatuximab, and the anti-Signaling lymphocytic activation molecule family member 7 antibody elotuzumab, all of which are used in their unconjugated formats. Single-chain variable fragments from antibodies also form a key element of the chimeric antigen receptors (CARs) in the B-cell maturation antigen (BCMA)-targeted CAR T-cell products idecabtagene vicleucel and ciltacabtagene autoleucel, which are approved in the advanced setting. Most recently, the bispecific anti-BCMA and T-cell-engaging antibody teclistamab has become available, again for patients with relapsed/refractory disease. Another format into which antibodies can be converted to exert anti-tumor efficacy is as antibody-drug conjugates (ADCs), and belantamab mafodotin, which also targets BCMA, represented the first such agent that gained a foothold in myeloma. Negative results from a recent Phase III study have prompted the initiation of a process for withdrawal of its marketing authorization. However, belantamab remains a drug with some promise, and many other ADCs targeting either BCMA or other plasma cell surface markers are in development and showing potential. This contribution will provide an overview of some of the current data supporting the possibility that ADCs will remain a part of our chemotherapeutic armamentarium against myeloma moving forward, and also highlight areas for future development.