Despite the significant improvement in survival outcomes of multiple myeloma (MM) over the past decade, it remains an incurable disease. Patients with triple-class refractory MM have limited treatment options and a dismal prognosis. Chimeric antigen receptor (CAR) T-cell therapy targeting B-cell maturation antigen has transformed the treatment armamentarium of relapsed/refractory MM (RRMM), with unprecedented overall response rates in this difficult-to-treat patient population. However, a significant proportion of patients ultimately relapse despite achieving deep remission. Several innovative approaches, including alternative/dual-antigen-specific CAR T-cell constructs, genetically engineered "off-the-shelf" CAR T cells, and strategies to counteract an immunosuppressive microenvironment, may dramatically reshape the field of CAR T-cell therapy in the future. These strategies are being actively investigated in preclinical and early clinical trial settings with the hopes of enhancing the durability of responses and, thereby, improving the overall survival of RRMM patients after CAR T-cell therapy.
© 2020 by The American Society of Hematology.