CAR T cell therapies for patients with multiple myeloma

Despite several major therapeutic advances, multiple myeloma (MM) remains largely incurable, indicating a need for novel therapies. Thus, considerable research interest exists in chimeric antigen receptor (CAR) T cells targeting BCMA, which is almost universally expressed on MM cells. In this Review, the authors describe the clinical experience with anti-BCMA CAR T cells and discuss several new directions of future research that might prolong the responses of patients receiving these therapies. Despite several therapeutic advances over the past decade, multiple myeloma (MM) remains largely incurable, indicating a need for new treatment approaches. Chimeric antigen receptor (CAR) T cell therapy works by mechanisms distinct from those of other MM therapies and involves the modification of patient or donor T cells to target specific cell-surface antigens. B cell maturation antigen (BCMA) is expressed only on plasma cells, a small subset of B cells and MM cells, which makes it a suitable target antigen for such therapies. At the time of writing, data from >20 clinical trials involving anti-BCMA CAR T cells have demonstrated that patients with relapsed and/or refractory MM can achieve objective responses. These early investigations have been instrumental in demonstrating short-term safety and efficacy; however, most patients do not have disease remission lasting >18 months. Attempts to reduce or delay the onset of relapsed disease are underway and include identifying additional CAR T cell target antigens and methods of enhancing BCMA expression on MM cells. Engineering CAR T cells to enhance both the activity and safety of treatment continues to be a promising avenue for improvement. In this Review we summarize data from clinical trials that have been carried out to date, describe novel antigens that could be targeted in the future, and highlight potential future innovations that could enhance the efficacy and/or reduce the toxicities associated with CAR T cell therapies.