[多发性骨髓瘤患者可溶性 B 细胞成熟抗原表达与靶向 B 细胞成熟抗原的嵌合抗原受体 T 细胞疗效之间相关性的临床分析]。

S Q Gao, J Mu, X Li, J Wang, R Cui, J Y Li, T Sui, Q Deng
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引用次数: 0

摘要

目的骨髓可溶性B细胞成熟抗原(sBCMA)表达对嵌合抗原受体(CAR)修饰的T细胞靶向B细胞成熟抗原(BCMA)在多发性骨髓瘤(MM)患者中的疗效和副作用的影响。方法:这项研究涉及29名复发或难治性MM(RRMM)患者,他们在2018年1月至2021年12月期间接受了人源化抗BCMA CAR-T细胞临床试验。通过流式细胞术检测并比较了抗BCMA CAR-T细胞治疗前后骨髓中sBCMA的表达。结果如下①BCMA CAR-T细胞治疗2个月后,20例患者(68.97%)获得总体应答(OR),9例患者病情稳定(SD)或出现矿化反应(MR)。20例OR患者骨髓中sBCMA的表达在治疗前高于治疗后[26 926(18 215,32 488)ng/L vs 9 968(6 634,11 459)ng/L;Pvs. 33 954(31 569,36 256)ng/L;P=0.145];CAR-T细胞治疗前OR患者的sBCMA表达低于MR和SD患者(P=0.005)。在所有 29 例 RRMM 患者的骨髓中,CAR-T 细胞峰值与 sBCMA 表达之间未发现明显的线性相关(R(2)=0.035,P=0.330)。在 0-1 级 CRS 组(13 名患者)和 2-4 级 CRS 组[16 名患者;32 045(18 742,40 801)ng/L vs 29 102(24 679,38 776)ng/L,P=0.879],0 级 ICANS 组(22 名患者)与 1-3 级 ICANS 组之间的差异也不大[7 名患者;30 073(19 375,40 065)ng/L vs 33 816(22 933,43 459)ng/L,P=0.763]。结论:骨髓中 sBCMA 的表达与 RRMM 患者接受 BCMA CAR-T 细胞疗法的疗效有关,但与不良反应的严重程度无显著相关性。它可作为这些患者接受 BCMA CAR-T 细胞疗法疗效的预测性生物标志物。
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[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].

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.

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