SOHO State-of-the-Art Updates and Next Questions | BCMA-Directed CAR T-Cells: Early Results and Future Directions.

Abstract

Despite continued advances that have led to improved survival of patients with multiple myeloma (MM) over the years, MM remains largely incurable with overall survival in patients who have progressed after proteasome inhibitor, immunomodulatory drug, and anti-CD38 monoclonal antibody therapy measured in months. Better understanding of the immunopathology of MM has led to the discovery of newer treatment targets like B-cell maturation antigen (BCMA). BCMA is a tumor necrosis factor receptor superfamily expressed on normal B-lymphocytes and malignant plasma cells with a vital role in proliferation, maturation, and differentiation of normal and malignant plasma cells. Antibody drug conjugates, chimeric antigen receptor (CAR) T-cells and bispecific T-cell engagers targeting the BCMA antigen are now available within and outside of clinical trials for treatment of triple class refractory MM. This review article focuses on the evolution, safety, efficacy, and limitations of BCMA-directed CAR T-cell therapies. It also discusses the challenges unveiled by the incorporation of these CAR T-cells in the treatment paradigm of MM and deliberates on the future of CAR T-cell therapy within MM.