Effective anti-BCMA retreatment in multiple myeloma

Abstract

The recent emergence of anti-B-cell maturation antigen (BCMA) therapies holds great promise in multiple myeloma (MM). These include chimeric antigen receptor (CAR) T cells, bispecific antibodies, and antibody-drug conjugates. Their development in clinical trials and further approval are changing the strategy for treating MM. Considering that a cure has not been reached, a central question in the coming years will be the possibility of using these therapies sequentially. Here, we report 2 cases of the serial use of anti-BCMA therapies with parallel monitoring of BCMA expression and anti-CAR antibodies. We further discuss recent data from clinical studies that have informed us about the different mechanisms of resistance to anti-BCMA therapies, including antigen escape, BCMA shedding, anti-drug antibodies, T-cell exhaustion, and the emergence of an immunosuppressive microenvironment. This knowledge will be essential to help guide the strategy of serial treatments with anti-BCMA therapies.