Efficacy and safety of chimeric antigen receptor (CAR)-T cell therapy in the treatment of relapsed and refractory multiple myeloma: a systematic-review and meta-analysis of clinical trials.

Background: Multiple myeloma (MM) is a malignant tumor originating from plasma cells in the bone marrow. The existing treatment methods can prolong the survival time of patients, but they still face the problems of myeloma relapse and refractory disease. Chimeric antigen receptor (CAR)-T cell therapy is a new cellular immunotherapy that can target and recognize antigens and kill tumor cells but the efficacy and safety data varied in different studies. We performed this systematic review and meta-analysis to understand its efficacy and safety. Methods: Literature published from January 2015 to November 2021 was obtained by searching the keywords "CAR-T", "CAR-T Cell", and "Multiple Myeloma" by computer using the Embase, PubMed, Web of Science, and Cochrane library databases according to the PICOS (Participants, Interventions, Comparisons, Outcomes, Study type) criteria. The quality of the literature was assessed by the Joanna Briggs Institute (JBI) Critical Appraisal Tool for prevalence studies. The complete response rate, the incidence of cytokine release syndrome (CRS) above grade 3, and the overall incidence of adverse reactions were used as the outcome indicators. The pooled rates were performed and analyzed using the R language toolkit. Results: A total of 10 studies including 353 study cases were included. Meta-analysis showed that the pooled complete response rate of CAR-T therapy in the treatment of MM was 0.55, 95% confidence interval (CI): (0.50, 0.60), the pooled incidence of CRS was 0.55, 95% CI: (0.50, 0.60), and the pooled incidence of serious adverse reactions was 0.92, 95% CI: (0.88, 0.95). Subgroup analysis was performed based on antigen types or costimulatory molecules, and there was no significant difference in the efficacy of CAR-T and the incidence of CRS between the two subgroups (P>0.05). Conclusions: As a new immunotherapy strategy with great potential, CAR-T has a significant effect in the treatment of MM, but its safety needs to be further improved. The types of costimulatory molecules and CAR-T antigens can affect its efficacy and safety.