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抗 PD-1/PD-L1 单克隆抗体治疗实体瘤患者的肾毒性:系统评价和荟萃分析。

Nephrotoxicity in patients with solid tumors treated with anti-PD-1/PD-L1 monoclonal antibodies: a systematic review and meta-analysis.

机构信息

Department of Nephrology, Hebei Key Laboratory of Vascular Calcification in Kidney Disease, Hebei Clinical Research Center for Chronic Kidney Disease, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050011, People's Republic of China.

出版信息

Invest New Drugs. 2021 Jun;39(3):860-870. doi: 10.1007/s10637-020-01039-5. Epub 2021 Jan 6.

DOI:10.1007/s10637-020-01039-5
PMID:33409896
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8068624/
Abstract

Background Programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1) have dramatically improved cancer therapy for many patients. Adverse kidney effects have been found to be an important complication but have unclear mechanisms. Methods We searched Embase, PubMed, and the Cochrane Library to identify potential eligible studies. All included studies were randomized controlled trials (RCTs) examining patients with solid tumors treated with anti-PD-1/PD-L1 monoclonal antibodies (mAbs) and/or chemotherapy. The relative risk (RR) was used to assess the risk of nephrotoxic events. Results We included 27 clinical trials (15,063 patients). Compared with chemotherapy, the RR of all-grade nephritis was significantly increased with anti-PD-1/PD-L1 mAbs (RR = 2.77, 95% CI: 1.09-6.99, P = 0.03). Furthermore, anti-PD-1/PD-L1 mAbs plus chemotherapy can significantly increase the RR of all-grade nephritis (RR = 2.99, 95% CI: 1.07-8.35, P = 0.04). There was also a significant increase in the RRs of all-grade increased blood creatinine (RR = 1.88, 95% CI: 1.24-2.86, P = 0.003) and acute kidney injury (AKI) (RR =3.35, 95% CI: 1.48-7.60, P = 0.004). Conclusions Anti-PD-1/PD-L1 mAbs can significantly increase nephrotoxicity in patients with solid tumors, especially when combined with chemotherapy. During the application of these drugs, we should remain aware of nephrotoxicity for better efficacy. Trial registration number and date of registration Not applicable.

摘要

背景

程序性死亡受体-1(PD-1)和程序性死亡配体 1(PD-L1)显著改善了许多患者的癌症治疗效果。已经发现,不良的肾脏影响是一种重要的并发症,但机制尚不清楚。

方法

我们在 Embase、PubMed 和 Cochrane 图书馆中搜索了可能的合格研究。所有纳入的研究均为检查接受抗 PD-1/PD-L1 单克隆抗体(mAb)和/或化疗治疗的实体瘤患者的随机对照试验(RCT)。相对风险(RR)用于评估肾毒性事件的风险。

结果

我们纳入了 27 项临床试验(15063 名患者)。与化疗相比,抗 PD-1/PD-L1 mAb 治疗的所有级别肾炎的 RR 显著增加(RR=2.77,95%CI:1.09-6.99,P=0.03)。此外,抗 PD-1/PD-L1 mAb 联合化疗可显著增加所有级别肾炎的 RR(RR=2.99,95%CI:1.07-8.35,P=0.04)。所有级别血肌酐升高(RR=1.88,95%CI:1.24-2.86,P=0.003)和急性肾损伤(AKI)(RR=3.35,95%CI:1.48-7.60,P=0.004)的 RR 也显著增加。

结论

抗 PD-1/PD-L1 mAb 可显著增加实体瘤患者的肾毒性,尤其是与化疗联合使用时。在应用这些药物时,我们应注意肾毒性,以获得更好的疗效。

注册号和注册日期

不适用。

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