Renal Toxicity in Patients Treated with Anti-Pd-1 Targeted Agents for Solid Tumors

Abstract

Aim

Immune checkpoint inhibitors of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) have recently entered in the therapeutic armamentarium of several types of cancer. Besides the survival benefit, the true revolution of these agents is the distinctive toxicity profile. We aim to assess the incidence and relative risk (RR) of renal toxicity (RT) in patients with solid tumors treated with monoclonal antibodies (mAbs) directed against PD-1/PD-L1.

Methods

By searching the MEDLINE/PubMed, Cochrane Library, and ASCO Meeting abstracts, prospective studies were identified. Combined RRs and 95% confidence intervals (CIs) were calculated using fixed- or random-effects methods.

Results

Eleven articles were selected for this analysis, with a total of 5,722 patients who were used to evaluate RT. The incidence of anti-PD-1-related RT of all-grades and high-grades was low (1.4% and 0.2%, respectively). However, compared to controls, treatment with PD-1 inhibitors was associated with a significant increased risk of any grade RT (RR = 1.85, 95% CI, 1.07-3.20; p = 0.03) but not high-grade RT (RR = 1.57, 95% CI, 0.56-4.36; p = 0.39). Pembrolizumab significantly increased the risk of any-grade RT (RR = 4.91, p = 0.01) compared to the control arm, and a significant difference was found between nivolumab and pembrolizumab for developing RT of any grade (p = 0.04). Conversely, no differences were identified between the type of prior treatment (prior platinum-containing chemotherapy regimen vs. nonplatinum containing regimen).

Conclusions

Immune-mediated RT is a rare adverse event that is generally low in severity. Compared to standard therapies, anti-PD-1 mAbs significantly increase the risk of any grade, without conditioning the risk of high-grade RT. The type of PD-1 inhibitor could affect the risk of developing any-grade RT, while prior therapy with platinum-containing regimens does not affect the risk of developing RT.