复发/难治性多发性骨髓瘤中可溶性 BCMA 表达与抗 BCMA CAR-T 细胞治疗近期/远期疗效及生存结局的相关性

This study aimed to investigate whether soluble B-cell maturation antigen (sBCMA) levels could be predictive biomarker for short-term and long-term therapeutic efficacy and survival outcomes following anti-BCMA CAR-T cell therapy in relapsed/refractory multiple myeloma (R/R MM).

We enrolled 29 R/R MM patients who received anti-BCMA CAR-T cell therapy. In short-term observation, proportion of MM cells, expression of B-cell maturation antigen (BCMA) and sBCMA in bone marrow (BM) were evaluated, along with adverse events, correlation between sBCMA levels and short-term efficacy or survival outcomes were evaluated. In long-term observation, expressions of sBCMA were observed up to 24 months after therapy or until disease progression again in patients who achieved an objective response (ORR).

Progression-free survival (PFS), overall survival (OS), correlation between sBCMA levels, and long-term outcomes were analyzed. In short-term observation, high expressions of sBCMA in BM were associated with poor efficacy of CAR-T cell therapy, while the proportion of MM cells in BM and BCMA expression in MM cells were not associated with poor efficacy of therapy.

After 2 months of infusion, sBCMA levels decreased significantly, especially in patients who obtained ORR. In long-term follow-up, for patients who achieved ORR, the sBCMA levels significantly increased again when their disease progressed once more.

Notably, R/R MM patients with extramedullary disease (EMD) demonstrated a higher likelihood of disease progression again. In patients achieved ORR, peaks of CAR-T cells correlated with proportion of MM cells, not with BCMA and sBCMA expression.

Additionally, sBCMA levels were independent of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) severity.

We suggest that sBCMA levels in BM might serve as a predictive biomarker for anti-BCMA CAR-T cell therapy efficacy prior to treatment and for disease progression during long-term monitoring. The trail register name is China Clinical Trial Register. URL are https://www. chictr. org. cn/bin/project/edit? pid=28999 and https://www. chictr. org. cn/bin/project/edit? pid=53962. Registration numbers are ChiCTR1800017051 and ChiCTR2000033925 .