Khan Israr, Khan Nida, Wolfson Natalie, Djebabria Kawthar, Rehman Mohammad Ebad Ur, Anwer Faiz
Department of Internal Medicine, HMH Palisades Medical Center, 7600 River Rd, North Bergen, NJ, 07047, USA.
Department of Internal Medicine, Jinnah Sindh Medical University, Karachi, Pakistan.
Clin Hematol Int. 2023 Jun;5(2-3):122-129. doi: 10.1007/s44228-023-00037-7. Epub 2023 Apr 3.
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.
嵌合抗原受体（CAR）T细胞疗法是一种专门针对癌细胞的新型免疫疗法，已被证明能在一些难治性血液系统恶性肿瘤中诱导持久缓解。然而，CAR T细胞疗法存在不良反应，如细胞因子释放综合征（CRS）、免疫效应相关神经毒性综合征（ICANS）、肿瘤溶解综合征（TLS）和急性肾损伤（AKI）等。关于CAR T细胞疗法对肾脏影响的研究并不多。在本综述中，我们总结了关于CAR T细胞疗法在已有肾功能不全/AKI患者以及因CAR T细胞疗法而发生AKI患者中的安全性的现有证据。CAR T细胞治疗后AKI的发生率为30%，各种病理生理机制，如CRS、噬血细胞性淋巴组织细胞增生症（HLH）、TLS、血清细胞因子和炎症生物标志物，均已显示发挥作用。然而，CRS通常被报告为潜在机制。总体而言，我们纳入研究中的18%患者在接受CAR T细胞治疗后发生了AKI，大多数病例经适当治疗后可逆转。虽然1期临床试验排除了有显著肾毒性的患者，但两项研究（Mamlouk等人和Hunter等人）报告了对依赖透析的难治性弥漫性大B细胞淋巴瘤患者的成功治疗，并证明CAR T细胞疗法和淋巴细胞清除（氟达拉滨/环磷酰胺）可以安全应用。
