CAR-T Therapy of Multiple Myeloma, Based on the Congresses ASH-2021 and ASCO-2022

Abstract

Current treatment of multiple myeloma (ММ) based on proteasome inhibitors, immunomodulating drugs, and monoclonal antibodies has, to a certain extent, reached the limit of its potential. Despite considerable clinical advance, ММ still remains a chronic incurable disease. Tumor-specific T-cell therapy with chimeric antigen receptor (CAR) is a new evolution step towards achieving MM cure. Today, B-cell maturation antigen (BCMA) is regarded as the primary target of CAR-T treatment of MM. This receptor is mainly expressed on the surface of tumor plasma cells in ММ as well as in B-cells of late differentiation stages and normal plasma cells. In 2021–2022, two CAR-T drugs, idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), were approved for clinical use in the USA and the European Union for patients with relapsed/refractory MM. The studies of these drugs yielded encouraging clinical results. Other antigen (GPRC5D, SLAMF7) cell-based drugs are now in early stages of development. The present review is concerned with latest advances in CAR-T therapy for MM reported at the recent congresses ASH-2021 and ASCO-2022. The review comprehensively discusses the results of the KarMMa (ide-cel, stage II) and CARTITUDE-1 (cilta-cel, stage IB/II) studies. It also provides historical background of CAR-Т cell generation as well as preclinical and on-going clinical trial data on MM. It outlines potential failure causes and prospects of further improvement of the new technology.of its potential. Despite considerable clinical advance, ММstill remains a chronic incurable disease. Tumor-specific T-cell therapy with chimeric antigen receptor (CAR) isa new evolution step towards achieving MM cure. Today,B-cell maturation antigen (BCMA) is regarded as the primary target of CAR-T treatment of MM. This receptor is mainlyexpressed on the surface of tumor plasma cells in ММ aswell as in B-cells of late differentiation stages and normalplasma cells. In 2021–2022, two CAR-T drugs, idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel(cilta-cel), were approved for clinical use in the USA andthe European Union for patients with relapsed/refractoryMM. The studies of these drugs yielded encouraging clinical results. Other antigen (GPRC5D, SLAMF7) cell-baseddrugs are now in early stages of development. The presentreview is concerned with latest advances in CAR-T therapyfor MM reported at the recent congresses ASH-2021 andASCO-2022. The review comprehensively discusses theresults of the KarMMa (ide-cel, stage II) and CARTITUDE-1(cilta-cel, stage IB/II) studies. It also provides historicalbackground of CAR-Т cell generation as well as preclinicaland on-going clinical trial data on MM. It outlines potentialfailure causes and prospects of further improvement of thenew technology.