首页|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

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

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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BCMACAR-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BCMACAR-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(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[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BCMACAR-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.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(R2=0.035,P=0.330).@No 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;30073(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.

Multiple myelomaSoluble B cell maturation antigenChimeric antigen receptor T cell

高舒荃、穆娟、李新、王嘉、崔蕊、李静怡、隋涛、邓琦

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南开大学第一中心医院血液科,天津 300192

多发性骨髓瘤 可溶性B细胞成熟抗原 嵌合抗原受体T细胞

天津市卫生健康委科研项目天津市卫生健康委科研项目中国临床肿瘤学会北京市希思科临床肿瘤学研究基金会项目中国临床肿瘤学会北京市希思科临床肿瘤学研究基金会项目中国临床肿瘤学会北京市希思科临床肿瘤学研究基金会项目

TJWJ2022XK021TJWJ2023ZD003Y-SY2021QN-0184Y-Young2022-0209Y-NCJH202201-0027

2024

10.3760/cma.j.cn121090-20231020-00220

中华血液学杂志
中华医学会

中华血液学杂志

CSTPCD北大核心
影响因子：1.17
ISSN：0253-2727
年,卷(期)：2024.45(4)