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CAR-T 细胞治疗在肾衰竭/急性肾损伤患者中的安全性:聚焦综述

英文原题:Safety of CAR-T Cell Therapy in Patients With Renal Failure/Acute Kidney Injury: Focused Review.

查看英文原题

Safety of CAR-T Cell Therapy in Patients With Renal Failure/Acute Kidney Injury: Focused Review.

PubMed 2023/04/03(内容时间) Clin Hematol Int

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中文摘要

CAR-T 可在部分难治性血液恶性肿瘤中引起持久缓解,但可能导致CRS、ICANS、肿瘤溶解综合征和急性肾损伤等不良反应。CAR-T 对肾脏影响的研究有限。本综述总结已有证据,关注治疗前已有肾功能不全或急性肾损伤者,以及治疗后发生急性肾损伤者的安全性。CAR-T 后急性肾损伤发生率约30%的报道中,CRS、噬血细胞性淋巴组织细胞增多症、肿瘤溶解、血清细胞因子及炎症标志物等多种机制可能参与,其中最常报告的机制是CRS。纳入研究中总体约18%患者治疗后发生急性肾损伤,多数在适当治疗后可逆。尽管I期试验排除显著肾毒性患者,Mamlouk和Hunter等两项研究报告了透析依赖的难治性弥漫大B细胞淋巴瘤患者成功接受CAR-T,并显示CAR-T 及氟达拉滨/环磷酰胺淋巴清除可安全实施。

展开英文摘要原文

Chimeric antigen receptor (CAR) T-cell therapy is novel immunotherapy targeting specifically cancerous cells, and has been shown to induce durable remissions in some refractory hematological malignancies.

However, CAR T-cell therapy has adverse effects, such as cytokine release syndrome (CRS), immune effector-associated neurotoxicity syndrome (ICANS), tumor lysis syndrome (TLS), and acute kidney injury (AKI), among others. Not many studies have covered the repercussions of CAR T-cell therapy on the kidneys.

In this review, we summarized the available evidence on the safety profile of CAR T-cell therapy in patients with pre-existing renal insufficiency/AKI and in those who develop AKI as a result of CAR T-cell therapy. With a 30% incidence of AKI post-CAR T-cell, various pathophysiological mechanisms, such as CRS, hemophagocytic lymphohistiocytosis (HLH), TLS, serum cytokines, and inflammatory biomarkers, have been shown to play a role.

However, CRS is commonly reported as an underlying mechanism.

Overall, 18% of patients in our included studies developed AKI after receiving CAR T-cell therapy, and most cases were reversible with appropriate therapy. While phase-1 clinical trials exclude patients with significant renal toxicity, two studies (Mamlouk et al. and Hunter et al.) reported successful treatment of dialysis-dependent patients with refractory diffuse large B-cell lymphoma, and demonstrated that CAR T-cell therapy and lymphodepletion (Flu/Cy) can be safely administered.

论文信息

作者
Khan I、Khan N、Wolfson N、Djebabria K、Rehman MEU、Anwer F
单位
Department of Internal Medicine, HMH Palisades Medical Center, 7600 River Rd, North Bergen, NJ, 07047, USA. israrkhan.dawar@gmail.com.Norway
文献类型
综述
期刊
Clinical hematology international2023 Jun
原文标识
PubMed 37010812 · DOI 10.1007/s44228-023-00037-7