Renal toxicities in immune checkpoint inhibitors with or without chemotherapy: An observational, retrospective, pharmacovigilance study leveraging US FARES database

Abstract

Background: Immune checkpoint inhibitors (ICIs) have elicited durable antitumor responses in multiple types of cancers. However, ICIs could also induce potential toxicities that involve all organs, including renal system. In this study, we aimed to conduct a comprehensive description of the ICIs-induced renal toxicities and the potential effects of chemotherapy.

Methods: We conducted a pharmacovigilance study based on US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database between 01 January 2014 and 30 June 2019. Disproportionality analysis was used to assess the association between ICIs and renal adverse events (AEs), including reporting odds ratio (ROR) and information component (IC). ROR₀₂₅ and IC₀₂₅ are, respectively, 95% confidence interval lower end of ROR and IC. If the value of ROR₀₂₅ exceeding one or IC₀₂₅ higher than zero, then a signal was considered statistically significant.

Results: A total of 30,602,758 reports were extracted from the database, with 4578 reports for ICIs-associated renal AEs. Renal AEs were more frequently reported in anti-PD-1/PD-L1 versus anti-CTLA-4 monotherapy group (ROR: 1.75, 95% CI: 1.52-2.01). Similarly, renal AEs were more commonly reported in ICIs polytherapy other than monotherapy group (ROR: 1.18, 95% CI: 1.10-1.27). Notably, ICIs plus chemotherapy strategies reported more renal toxicities compared to sole ICIs regimens (ROR: 1.30, 95% CI: 1.17-1.45), whereas exhibited lower fatality outcome rates. Importantly, acute kidney injury (1139, 24.88%) and renal failure (464, 10.14%) were the top two most commonly reported ICIs-associated renal AEs, and also observed with the top two highest level of fatality outcome rates.

Conclusions: A spectrum of renal AEs was detected in ICIs regimens and could be reinforced by ICIs combination. Compared to sole ICIs regimens, ICIs plus chemotherapy strategy reported more renal toxicities but lower fatality outcome rates. With the increasing popularity of ICIs especially combination strategies, it is vital important for clinicians to guarantee balance between durable clinical effects and potential renal toxicities in latest immunotherapy strategies.

Keywords: FAERS database; chemotherapy; disproportionality analysis; immune checkpoint inhibitors; renal toxicity.