CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Safety of CAR-T Cell Therapy in Patients With Renal Failure/Acute Kidney Injury: Focused Review.
Safety of CAR-T Cell Therapy in Patients With Renal Failure/Acute Kidney Injury: Focused Review.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
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。
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.
在 PubMed 查看 → 出版商原文(DOI) 全文 PDF(PMC)· 可下载 治疗专题与资料阅读指南 资料来源与翻译说明 报告译文或资料问题 →
MEMBER ACCOUNT
登录成功会直接打开下一页。