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

• Published in: Investigational new drugs Vol. 39; no. 3; pp. 860 - 870
• Main Authors: Li, Han, Xu, Jinsheng, Bai, Yaling, Zhang, Shenglei, Cheng, Meijuan, Jin, Jingjing
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.06.2021; Springer Nature B.V
• Subjects: Antibodies, Monoclonal - adverse effects; B7-H1 Antigen - antagonists & inhibitors; Chemotherapy; Clinical trials; Creatinine; Humans; Immune Checkpoint Inhibitors - adverse effects; Kidney Diseases - chemically induced; Kidneys; Medicine; Medicine & Public Health; Meta-analysis; Monoclonal antibodies; Neoplasms - drug therapy; Nephritis; Oncology; PD-1 protein; PD-L1 protein; Pharmacology/Toxicology; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Randomized Controlled Trials as Topic; Review; Solid tumors; Tumors; Anti-PD-1/PD-L1 monoclonal antibodies; Chemotherapy; Solid tumors; Nephrotoxicity; Meta-analysis
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1007/s10637-020-01039-5

Summary 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.