Correlation between the expression of BCMA/soluble BCMA and the efficacy of BCMA CAR-T cell therapy in relapsed/refractory multiple myeloma

Anti-B cell maturation antigen (anti-BCMA) CAR T cell therapy has led to prolonged survival and response rates of 64-85% in patients with relapsed/refractory multiple myeloma (R/R MM). In a study of 29 R/R MM patients receiving anti-BCMA CAR T cell therapy, we aimed to identify predictors of pre-treatment efficacy and side effects. We observed multiple myeloma (MM) cells in bone marrow (BM), BCMA expression in MM cells, and soluble BCMA (sBCMA) levels in BM before and after therapy. Clinical response, CAR-T cell proportions, cytokine levels, and adverse events (AEs) were monitored during therapy. Twenty patients (68.97%) experienced an objective response rate (ORR) to the therapy. Before CAR-T cell therapy, there were no differences in the proportions of MM cells or BCMA expression between the ORR group and the MR+SD group, but sBCMA levels were higher in the MR+SD group compared to the ORR group. After therapy, BCMA and sBCMA expressions were lower in the ORR group than in the MR+SD group. In patients who achieved ORR, the peak levels of CAR-T cells correlated with the proportion of MM cells. IL-6 levels were correlated with the proportion of MM cells and sBCMA expressions. There were no differences in the proportion of MM cells, BCMA expressions, or sBCMA expressions between the grade 0-1 cytokine release syndrome (CRS) group and the grade 2-4 CRS group. The proportion of MM cells and BCMA expressions were lower in the grade 0 immune effector cell-associated neurotoxic syndrome (ICANS) group compared to the grade 1-3 ICANS group. There was no correlation between BCMA expression in MM cells and sBCMA levels in BM. Interestingly, high sBCMA levels in BM impacted efficacy, while the proportions of MM cells in BM and BCMA expression in MM cells did not. Therefore, we suggest that sBCMA levels in BM could be used as a predictor of the efficacy of anti-BCMA CAR T cell therapy, but further clinical verification is needed (ChiCTR2000033925).