Objective: The effect of bone marrow soluble B cell maturation antigen (sBCMA) expression on the efficacy and side effects of chimeric antigen receptor (CAR) -modified T-cell-targeting B cell maturation antigen (BCMA) in patients with multiple myeloma (MM) . Methods: This study involved 29 patients with relapsed or refractory MM (RRMM) who received humanized anti-BCMA CAR-T cell clinical trials from January 2018 to December 2021. The expression of sBCMA in bone marrow before and after anti-BCMA CAR-T cell treatment was detected by flow cytometry and compared. Results: ①Two months after BCMA CAR-T cell treatment, 20 patients (68.97%) achieved an overall response (OR), whereas nine patients had stable disease (SD) or miner emission (MR). ②The expression of sBCMA in the bone marrow of 20 patients with OR was higher before treatment than after [26 926 (18 215, 32 488) ng/L vs 9 968 (6 634, 11 459) ng/L; P<0.001]; no significant difference was observed in patients with MR and SD [41 187 (33 816, 47 046) ng/L vs. 33 954 (31 569, 36 256) ng/L; P=0.145]; sBCMA expression in patients with OR before CAR-T cell treatment was lower than in patients with MR and SD (P=0.005). ③No significant linear correlation was found between the peak value of CAR-T cells and sBCMA expression in the bone marrow of all 29 patients with RRMM (R(2)=0.035, P=0.330). ④No significant difference in sBCMA expression was found between grades 0-1 CRS group (13 patients) and grades 2-4 CRS group [16 patients; 32 045 (18 742, 40 801) ng/L vs 29 102 (24 679, 38 776) ng/L, P=0.879], nor between grade 0 ICANS group (22 patients) and grade 1-3 ICANS group [seven patients; 30 073 (19 375, 40 065) ng/L vs 33 816 (22 933, 43 459) ng/L, P=0.763]. Conclusion: sBCMA expression in the bone marrow is related to the efficacy of BCMA CAR-T cell therapy in patients with RRMM, but is not significantly correlated with the severity of adverse events. It may serve as a predictive biomarker for the efficacy of BCMA CAR-T cell therapy in these patients.
目的： 探索多发性骨髓瘤（MM）患者骨髓可溶性B细胞成熟抗原（sBCMA）表达对靶向B细胞成熟抗原（BCMA）的嵌合抗原受体T细胞（CAR-T细胞）治疗疗效及安全性的影响。 方法： 以2018年1月至2021年12月接受人源化抗BCMA CAR-T细胞临床试验的29例复发/难治MM（RRMM）患者为研究对象。流式细胞术检测抗BCMA CAR-T细胞治疗前后骨髓sBCMA的表达并进行差异比较。 结果： ①BCMA CAR-T细胞治疗2个月，20例（68.97%）患者获得总体反应（OR），9例患者仅为病情稳定（SD）或微小缓解（MR）。②20例OR组患者骨髓sBCMA表达治疗前高于治疗后[26 926（18 215, 32 488）ng/L对9 968（6 634, 11 459）ng/L，P<0.001]；而MR+SD组患者骨髓sBCMA表达治疗前后差异无统计学意义[41 187（33 816, 47 046）ng/L对33 954（31 569, 36 256）ng/L，P=0.145]；CAR-T细胞治疗前骨髓sBCMA表达OR组低于MR+SD组患者（P=0.005）。③全部29例RRMM患者CAR-T细胞峰值与骨髓sBCMA表达无明显线性相关性（R(2)=0.035，P=0.330）。④sBCMA表达水平与CAR-T细胞治疗不良事件严重程度的相关性：0~1级细胞因子释放综合征（CRS）组（13例）与2~4级CRS组（16例）比较骨髓sBCMA表达差异无统计学意义[32 045（18 742, 40 801）ng/L对29 102（24 679, 38 776）ng/L，P=0.879]；0级免疫效应细胞相关神经毒性综合征（ICANS）组（22例）与1~3级ICANS组（7例）比较骨髓sBCMA表达差异无统计学意义[30 073（19 375, 40 065）ng/L对33 816（22 933, 43 459）ng/L，P=0.763]。 结论： 骨髓sBCMA表达与RRMM患者接受BCMA CAR-T细胞治疗的疗效有关，但与不良事件严重程度无显著相关性。或可作为RRMM患者接受BCMA CAR-T细胞治疗的疗效预测标志物。.
Keywords: Chimeric antigen receptor T cell; Multiple myeloma; Soluble B cell maturation antigen.