SOHO State of the Art Updates and Next Questions: T-Cell-Directed Immune Therapies for Multiple Myeloma: Chimeric Antigen Receptor-Modified T Cells and Bispecific T-Cell-Engaging Agents

Therapeutic monoclonal antibodies targeting SLAMF7 and CD38 are the first classes of targeted immunotherapies approved for multiple myeloma, a cancer of plasma cells. These agents are effective, particularly in combination with the immunomodulatory drugs lenalidomide and pomalidomide. The next generation of myeloma immunotherapy under investigation consists of T-cell-directed strategies designed to promote cytotoxic activity against myeloma cells, as embodied by chimeric antigen receptor-modified T cells (CAR-T) and bispecific T-cell-engaging agents. Early clinical trial results with these classes of therapies are promising, with high response rates reported. These strategies appear to be strong activators of immunoresponse, and adverse effects, particularly cytokine release syndrome and cytokine-related encephalopathic syndrome, are common. Ongoing research explores the optimal disease setting and combination therapies for these agents. These studies provide an unprecedented opportunity to understand the mechanisms of action and their relations to adverse effects and resistance to therapy.