Novel Therapies in BCMA-exposed Relapsed/Refractory Multiple Myeloma: The Anti-BCMA Therapy-refractory Patient

Abstract

Multiple myeloma (MM) is a haematologic malignancy resulting from the malignant overgrowth of monoclonal plasma cells in the bone marrow. Nearly 35,000 new cases are expected in the USA each year. In the last two decades there have been many clinical advances with the approvals of many new drugs and their combinations, which have improved survival statistics. Despite this, MM remains incurable, and patients with relapsed/refractory MM remain vulnerable. The development of chimeric antigen receptor T-cell (CAR-T) therapy has shown promising results utilizing several target antigens; of note, B-cell maturation antigen (BCMA) is most prominent, due to its universal expression on the surface of malignant plasma cells. While anti-BCMA CAR-T therapies are inspiring, most patients eventually relapse and require further treatment. With these patients progressing through standard-of-care therapies, and more recently through novel anti-BCMA CAR-T therapies, we are faced with exploring novel treatment regimens to challenge their diseases. In this review, we discuss the different mechanisms of resistance to anti-BCMA therapies, effective retreatment with anti-BCMA-targeted therapies in MM, and advances in therapies utilizing other novel targets for patients who have progressed through anti-BCMA treatment.