Options at the time of relapse after anti -BCMA therapy

B-cell maturation antigen (BCMA)-directed therapies, including antibody-drug conjugates, bispecific antibodies (BsAbs), and chi me ric anti gen recep tor T cells (CARTs), have shown remark able effi cacy in patients with late- line mye loma with prior exposure to immunomodulatory agents, proteasome inhibitors, and anti-CD38 antibodies. However, optimal sequenc ing of these agents remains to be deter mined, and man age ment of these patients once they relapse has become a new unmet need. Fortunately, there are mul ti ple options with dem on strated activ ity after anti- BCMA ther apy, including a different BCMA-directed therapy, non-BCMA-directed CARTs and BsAbs, novel non-T-cell-engaging drugs, and stan dard trip let / qua dru plet reg i mens or sal vage stem cell trans plant. Factors to con sider when choos ing a next ther apy after anti-BCMA therapy include patient characteristics and preferences, prior therapies and toxicities, disease biology, tim ing from last anti- BCMA ther apy, and, in the future, BCMA expres sion and immune pro fil ing. While cur rent data are limited to retrospective studies and small prospective cohorts, the serial use of T-cell-engaging therapies looks particu larly prom is ing, espe cially as BCMA - directed ther a pies move up ear lier in the mye loma treat ment course and additional CARTs and BsAbs against alter na tive tar gets (eg, G pro tein - cou pled recep tor, fam ily C, group 5, mem ber D and Fc receptor-homolog 5) become available. Going forward, ongoing prospective studies, large real-world data sets, and bet ter tools to inter ro gate anti gen expres sion and immune cell fi t ness hope fully will pro vide fur ther insight into how to best individualize therapy for this difficult-to-treat population.