Bispecific antibody and chimeric antigen receptor (CAR) modified T-cell in the treatment of multiple myeloma: where do we stand today?

Abstract

Although the prognosis of patients with multiple myeloma (MM) has been significantly improved by the introduction of proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies, MM is still considered an incurable disease in the vast majority of the patients. In recent years, T-cell based immunotherapy represents a novel treatment strategy for relapsed/refractory (RR) MM. So far, chimeric antigen receptor (CAR) modified T-cells and bispecific T-cell engaging antibodies (bsAb) have shown promising anti-MM efficacy and manageable safety profile within clinical trials, and B-cell maturation antigen (BCMA) is the most commonly used immune target for T-cell based immunotherapies in MM. To date, several CAR T-cell and bsAb products have already been approved for the treatment of RRMM, leading to a paradigm shift in the MM therapy and providing a potential curative option. In this review, we provide a summary of mechanisms of action, immune targets, selected clinical data, resistance mechanisms and therapy sequencing of CAR T-cell and bsAb in MM.