BCMA靶向的嵌合抗原受体T细胞治疗复发/难治多发性骨髓瘤患者发生肿瘤溶解综合征的危险因素

Risk factors of tumor lysis syndrome in relapsed/refractory multiple myeloma patients undergoing BCMA CAR-T cell therapy

目的:探究应用B细胞成熟抗原(BCMA)靶向的嵌合抗原受体(CAR)T细胞治疗的复发/难治多发性骨髓瘤(MM)患者发生肿瘤溶解综合征(TLS)的危险因素。方法:收集浙江大学医学院附属第一医院2018年7月至2021年12月共99例接受BCMA靶向的CAR-T细胞治疗MM患者的临床资料,通过单因素分析及多因素logistic回归分析患者接受BCMA靶向的CAR-T细胞治疗后发生TLS的危险因素。结果:99例患者中,17例发生TLS(TLS组),发生率为17.2%,发生时间为BCMA靶向的CAR-T细胞输注后(8.9±3.0)d。TLS组均出现TLS相关临床表现,其中出现肾功能不全17例,心律失常8例。TLS组均发生细胞因子释放综合征(CRS),发生时间为BCMA靶向CAR-T细胞输注后1.0(1.0,6.5)d,其中3~4级CRS 13例。TLS组治疗前血肌酐、血尿酸较非TLS组高,3~4级CRS患者的比例也高于非TLS组(P<0.01或P<0.05)。Logistic回归分析结果显示,高血肌酐水平(OR=1.015,P<0.01)和严重CRS(OR=9.371,P<0.01)是TLS发生的独立危险因素。结论:接受BCMA靶向的CAR-T细胞治疗的复发/难治MM患者具有较高的TLS发生率,高血肌酐水平和严重CRS是TLS的主要危险因素,临床可通过降低血肌酐、控制CRS严重程度预防TLS的发生。

Objective:To investigate the risk factors of tumor lysis syndrome(TLS)in relapsed/refractory multiple myeloma(MM)patients undergoing B-cell maturation antigen(BCMA)chimeric antigen receptor(CAR)T cell therapy.Method:The clinical data of 99 relapsed/refractory MM patients receiving BCMA CAR-T cell therapy in the First Affiliated Hospital,Zhejiang University School of Medicine from July 2018 to December 2021 were collected in this study.Univariate analysis and multivariate logistic regression were performed to evaluate the risk factors of TLS following BCMA CAR-T cell therapy.Results:Among the 99 patients,TLS occurred in 17 cases(17.2%)with an onset time of(8.9±3.0)d after BCMA CAR-T cell therapy.All TLS patients developed TLS-related clinical manifestations,including 17 cases with renal dysfunction,8 cases with arrhythmia.All TLS patients developed cytokine release syndrome(CRS)with an onset of 1.0(1.0,6.5)d after CAR-T cell therapy,and 13 cases developed grade 3–4 CRS.The levels of serum uric acid,serum creatinine and the ratio of cases with grade 3–4 CRS were significantly higher in TLS patients than in non-TLS patients(all P<0.05).Multivariate logistic regression revealed that serum creatinine(OR=1.015,P<0.01)and severe CRS(OR=9.371,P<0.01)were independent risk factors of TLS.Conclusions:Relapsed/refractory MM patients undergoing BCMA CAR-T therapy shows high incidence of TLS,which are related to elevated levels of serum creatinine and severe CRS.TLS can be prevented clinically by reducing serum creatinine and controlling CRS severity.