Anti-BCMA CAR T-cell therapy in multiple myeloma: can we do better?

Despite a substantial survival improvement and the availability of many new drugs in the last 2 decades, multiple myeloma (MM) remains largely incurable. Immunotherapeutic approaches are changing the current landscape in MM with B-cell maturation antigen (BCMA) as one of the most promising target antigens. Chimeric antigen receptor (CAR) T-cell therapy targeting BCMA produced unprecedented results in heavily pretreated relapsed and/or refractory MM. Data on more than 300 MM patients treated with anti-BCMA directed CAR T cells are available and these numbers are rapidly increasing. The response rate and the depth of responses induced by anti-BCMA CAR T cells are impressive; however, the majority of patients eventually relapse. Understanding the underlying mechanisms of response and resistance in treated MM patients will be critical to the rational development of this therapy. Moreover, the ideal place of this therapy in the treatment paradigm for MM is an important question that needs biological and clinical correlative data to help elucidate. T-cell-related, tumor-related and microenvironmental factors may play a role in the efficacy of anti-BCMA CAR T-cell therapy. In this review we summarize key clinical and correlative data on anti-BCMA CAR T-cell therapy. Based on available data we will try to highlight opportunities to further optimize this potential game-changing therapy for MM.