Emerging Clinical and Research Issues in the Era of CAR-T Cell Therapy for Multiple Myeloma

Abstract

 Recently, the anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR)-T cell therapy has opened a new avenue of the treatment for patients with tiple class-exposed (TCE) multiple myeloma (MM) who has been previously exposed to proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibody. In Japan, two anti-BCMA CAR-T cell therapies, i.e., Idecabtagene vicleucel (Ide-cel) and Ciltacabtagene autoleucel (Cilta-cel), have been approved for the treatment of TCE-MM in 2022, and have shown higher response rates and longer disease control periods compared with pre-existing treatment strategies with various anti-MM agents; however, it remains still difficult to provide a cure of MM by anti-BCMA CAR-T cell therapy with the currently available setting. This article will review the clinical efficacies and limitations of Ide-cel and Cilta-cel against TCE-MM, summarizes the known mechanisms of resistance to anti-BCMA CAR-T cell therapy in MM, and discuss the future perspectives for the new strategies, including the use of anti-BCMA CAR-T in the earlier line of therapy, the challenging strategies for T cell manipulation, the development of non-BCMA-targeted CAR-T cell therapy, and the strategies to manipulate immunosuppressive components in the tumor immune microenvironment in MM.