骨髓可溶性B细胞成熟抗原表达在多发性骨髓瘤患者中作为BCMA CAR-T细胞疗效预测指标的研究

Clinical analysis of the correlation between the expression of soluble B cell maturation antigen and the efficacy of chimeric antigen receptor T cell targeting B cell maturation antigen in patients with multiple myeloma

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[26926(18215,32488)ng/L对9968(6634,11459)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[41187(33816,47046)ng/L对33954(31569,36256)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(R2=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[32045(18742,40801)ng/L对29102(24679,38776)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[30073(19375,40065)ng/L对33816(22933,43459)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。

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.Results①Two 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[26926(18215,32488)ng/L vs 9968(6634,11459)ng/L;P<0.001];no significant difference was observed in patients with MR and SD[41187(33816,47046)ng/L vs.33954(31569,36256)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(R2=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;32045(18742,40801)ng/L vs 29102(24679,38776)ng/L,P=0.879],nor between grade 0 ICANS group(22 patients)and grade 1-3 ICANS group[seven patients;30073(19375,40065)ng/L vs 33816(22933,43459)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.