CAR-T cells immunotherapy in multiple myeloma: Present and future

Despite recent therapeutic advances, multiple myeloma remains an incurable disease and the therapeutic options currently available are insufficient in refractory patients. Chimeric antigen receptor (CAR)-expressing T cells are an innovative form of adoptive cell therapy in which T cells are reprogrammed to induce an anti-tumor response. Following the successful use of CAR-T cells in the treatment of other B-cell malignancies, CAR-T-based strategies which target the B cell maturation antigen (BCMA) on the surface of tumor plasma cell are now being used in MM patients. Idecabtagene vicleucel (ide-cel), an anti-BCMA CAR-T which has shown impressive efficacy in heavily pretreated patients, is now approved by both the FDA and EMA and is available in France through a temporary use authorization (ATU) status. However, relapses seem inevitable and strategies to delay the time to progression are being investigated. These include strategies to improve the functional persistence of CAR-T in vivo by enriching for a T memory profile and reducing their immunogenicity. In addition, since changes in BCMA expression may decrease the activity of CAR-T cells in tumor plasma cells, approaches to minimize this escape are also being studied. Finally, antigens other than BCMA on the surface of plasma cells could constitute new targets of interest for recognition by CAR-T cells. The development of CAR-T-based therapies in myeloma could lead to multiple therapeutic innovations and holds promise for eventual prolonged remissions or even cure.