摘要
目的:探究B细胞成熟抗原(BCMA)靶向的嵌合抗原受体(CAR)T细胞治疗复发/难治多发性骨髓瘤过程中患者发生急性肾损伤(AKI)的相关危险因素。方法:收集2018年7月至2021年12月在浙江大学医学院附属第一医院接受BCMA靶向的CAR-T细胞治疗的99例多发性骨髓瘤患者的临床资料。观察化疗预处理前后和CAR-T细胞输注后患者肾功能的动态变化,并采用logistic回归分析AKI发生的独立危险因素。结果:BCMA靶向的CAR-T细胞治疗过程中共有25例患者发生AKI,AKI发生率为25.3%,中位发生时间为8.0(5.5,11.0)d,其中AKI 1期2例(8.0%),AKI 2期3例(12.0%),AKI 3期9例(36.0%)。多因素logistic回归分析结果显示,化疗预处理后的血清肌酐(SCr)水平(OR=1.020,P<0.001)和细胞因子释放综合征(CRS)的严重程度(OR=6.501,P<0.01)与AKI的发生密切相关。化疗预处理后SCr水平预测AKI的曲线下面积为0.800(95%CI:0.694~0.904,P<0.001),最大约登指数为0.528,其所对应的截断值为83.0μmol/L,预测敏感度为72.0%,特异度为80.8%。3~4级CRS的患者AKI发生率为39.1%,而CRS低于3级的患者AKI发生率为13.2%,差异有统计学意义(χ^(2)=8.767,P<0.01)。结论:接受BCMA靶向的CAR-T细胞治疗的多发性骨髓瘤患者AKI多发生于CAR-T细胞输注后的15.0 d内,表现为一过性的严重肾功能损害。化疗预处理后存在肾功能异常的患者应警惕AKI的发生,同时在CAR-T细胞治疗期间须注意防治CRS。
Objective:To explore the risk factors of acute kidney injury(AKI)during B cell maturation antigen(BCMA)chimeric antigen receptor(CAR)T cell therapy in patients with relapsed/refractory multiple myeloma(MM).Methods:The clinical data of 99 patients with relapsed/refractory MM who received BCMA CAR-T cell therapy in the First Affiliated Hospital of Zhejiang University School of Medicine from July 2018 to December 2021 was retrospectively analyzed.Dynamic changes of renal function before and after chemotherapy preconditioning and after CAR-T cell infusion were observed.Logistic regression was used to analyze the independent risk factors associated with the occurrence of AKI.Results:Among 99 patients,the AKI occurred in 25 cases with an incidence rate of 25.3%,and the median time was 8.0(5.5,11.0)d.The AKI grade 1,2 and 3 accounted for 8.0%,12.0%and 36.0%,respectively.Logistic regression analysis showed that serum creatinine(SCr)after chemotherapy preconditioning(OR=1.020,P<0.001),and the grade of cytokine release syndrome(CRS)(OR=6.501,P<0.01)were independent risk factors for AKI during treatment.The area under the ROC curve(AUC)of SCr after chemotherapy preconditioning in predicting AKI was 0.800(95%CI:0.694–0.904,P<0.001);using 83.0μmol/L as cut-off value,the sensitivity,specificity and Youden index of SCr were 72.0%,80.8%and 0.528,respectively.The incidence of AKI in patients with grade 3–4 CRS was 39.1%,while that was 13.2%in patients with CRS<grade 3(χ^(2)=8.767,P<0.01).Conclusions:AKI mostly occurred within 15.0 d after CAR-T cell infusion,causing transient severe renal damage.Patients with abnormal renal function after chemotherapy preconditioning should be alert to the occurrence of AKI,and attention should be paid to the management of the CRS.
作者
吕雨琦
张明明
魏国庆
丁淑怡
胡永仙
黄河
LYU Yuqi;ZHANG Mingming;WEI Guoqing;DING Shuyi;HU Yongxian;HUANG He(Bone Marrow Transplantation Center,the First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China;Liangzhu Laboratory,Zhejiang University Medical Center,Hangzhou 311121,China;Institute of Hematology,Zhejiang University,Hangzhou 310058,China;Zhejiang Provincial Laboratory for Stem Cell and Immune Therapy,Hangzhou 310058,China)
出处
《浙江大学学报（医学版）》
CAS
CSCD
北大核心
2022年第2期137-143,共7页
Journal of Zhejiang University(Medical Sciences)
基金
国家自然科学基金(81730008,81870153)。
