CAR-T cells for the treatment of relapsed/refractory multiple myeloma in 2022: efficacy and toxicity

 Martin Krejci, Zdenek Adam, Marta Krejci, Ludek Pour, Viera Sandecka, Martin Stork

Abstract:

Chimeric antigen receptor (CAR)-T cells are a new treatment modality in various hematological malignancies, including relapsed/refractory multiple myeloma (RRMM). RRMM patients have a poor prognosis, and their treatment options are limited. Currently available data from clinical trials on CAR-T cell therapy have demonstrated efficacy and manageable toxicity in RRMM. The CAR-T cells in RRMM mostly focus on already known cellular targets, such as B-cell maturation antigen (BCMA). CAR-T cells focusing on other targets have been analyzed in various clinical trials as well. Cytokine release syndrome (CRS), specific neurotoxicity, and hematological toxicity are the main adverse events (AE); according to the clinical trials, they are mostly mild with a low incidence of grade 3 or higher toxicities. The autologous CAR-T cell therapy against BCMA (ide-cel and cilta-cel) shows the best efficacy with an overall response rate and a median progression-free survival in RRMM. Both ide-cel and cilta-cel have already been approved by the FDA. Currently, the main controversies in the routine use of CAR-T cells are high treatment costs and unknown long-term efficacy. In this review, we summarize the current overview of CAR-T cell therapies in RRMM in 2021 with various targets for CAR-T cells and their efficacy, safety, and possible limitations. Future prospective clinical trials are needed to clarify the optimal role of CAR-T cells in MM therapy.