Non-BCMA targeted CAR-T cell therapies for multiple myeloma

Despite the emergence of new strategies in recent years, multiple myeloma (MM) is still an incurable disease with poor outcome. As a new treatment, chimeric antigen receptor (CAR-) T cell therapy brought exciting news to patients with relapsed or refractory MM. B-cell maturation antigen (BCMA) is ubiquitously expressed on the surface of myeloma cells and is considered an “ideal” target of CAR-T cell. BCMA-targeted CAR-T cell therapies achieved remarkable efficacy in relapsed or refractory MM patients in several clinical trials. However, some patients had no response or relapsed after BCMA targeted CAR-T cell therapy. Myeloma cells also express other surface markers which might be used as targets for CAR-T cell therapy. Encouragingly, CAR-T cells targeting these non-BCMA markers are being tested in clinical trials or under preclinical investigation, already showing some promising results. In this review, we summarized and provided an update of these advances.