<strong>BCMA</strong>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急性肾损伤的危险因素

doi:10.3724/zdxbyxb-2022-0035

浙江大学学报（医学版）

2022, Vol. 51

Issue (2): 137-143 DOI: 10.3724/zdxbyxb-2022-0035

专题报道

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急性肾损伤的危险因素

吕雨琦^1,^2,^3,⁴,张明明^1,^2,^3,⁴,魏国庆^1,^2,^3,⁴,丁淑怡¹,胡永仙^1,^2,^3,^4,*(

),黄河^1,^2,^3,^4,*(

)

1. 浙江大学医学院附属第一医院骨髓移植中心，浙江杭州 310003
2. 浙江大学医学中心良渚实验室，浙江杭州 311121
3. 浙江大学血液学研究所，浙江杭州 310058
4. 浙江省干细胞与细胞免疫治疗工程实验室，浙江杭州 310058

Risk factors of acute kidney injury during BCMA CAR-T cell therapy in patients with relapsed/refractory multiple myeloma

LYU Yuqi^1,^2,^3,⁴,ZHANG Mingming^1,^2,^3,⁴,WEI Guoqing^1,^2,^3,⁴,DING Shuyi¹,HU Yongxian^1,^2,^3,^4,*(

),HUANG He^1,^2,^3,^4,*(

)

1. Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China;
2. Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou 311121, China;
3. Institute of Hematology, Zhejiang University, Hangzhou 310058, China;
4. Zhejiang Provincial Laboratory for Stem Cell and Immune Therapy, Hangzhou 310058, China

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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83.0?μmol/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（χ²=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。

关键词： 多发性骨髓瘤; 嵌合抗原受体T细胞; B细胞成熟抗原; 急性肾损伤; 细胞因子释放综合征; 危险因素

Abstract:

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 83.0?μmol/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 (χ²=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.

Key words: Multiple myeloma Chimeric antigen receptor T cell B cell maturation antigen Acute kidney injury Cytokine release syndrome Risk factor

收稿日期: 2022-02-14 出版日期: 2022-08-02

CLC:

R733

基金资助: 国家自然科学基金（81730008，81870153）

通讯作者: 胡永仙,黄河 E-mail: 1313016@zju.edu.cn

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引用本文:

吕雨琦,张明明,魏国庆,丁淑怡,胡永仙,黄河. 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急性肾损伤的危险因素[J]. 浙江大学学报（医学版）, 2022, 51(2): 137-143.

LYU Yuqi,ZHANG Mingming,WEI Guoqing,DING Shuyi,HU Yongxian,HUANG He. Risk factors of acute kidney injury during BCMA CAR-T cell therapy in patients with relapsed/refractory multiple myeloma. J Zhejiang Univ (Med Sci), 2022, 51(2): 137-143.

链接本文:

https://www.zjujournals.com/med/CN/10.3724/zdxbyxb-2022-0035 或 https://www.zjujournals.com/med/CN/Y2022/V51/I2/137

表 1 是否发生AKI的复发/难治多发性骨髓瘤患者BCMA靶向的CAR-T细胞治疗期间估算肾小球滤过率和血清肌酐水平比较

表 2 复发/难治多发性骨髓瘤患者BCMA靶向的CAR-T细胞治疗期间发生AKI危险因素的单因素logistic回归分析结果

表 3 复发/难治多发性骨髓瘤患者BCMA靶向的CAR-T细胞治疗期间发生AKI危险因素的多因素logistic回归分析结果

图 1 化疗预处理后SCr水平对复发/难治多发性骨髓瘤患者BCMA靶向的CAR-T细胞治疗期间发生AKI的预测价值SCr：血清肌酐；BCMA：B细胞成熟抗原；CAR：嵌合抗原受体；AKI：急性肾损伤.

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