Severe renal and pancreatic toxicities associated with ipilimumab and nivolumab combination therapy in non-small cell lung cancer: a pharmacovigilance analysis of the FDA adverse event reporting system.

Authors

Jiongrui Cao, Li Peng, Jin Yang, Gang Yin, Ping Ke, Jifa Zhang, Min Su, Yun Gao, Yuehui Zhang

Published in

Frontiers in immunology. Volume 17. Pages 1854177. Epub Jun 17, 2026.

Abstract

Ipilimumab plus nivolumab (Ipi+Nivo) has become a standard therapy for advanced non-small cell lung cancer (NSCLC), yet severe organ-specific toxicities remain inadequately characterized. This study aimed to characterize severe renal and pancreatic toxicities associated with Ipi+Nivo combination therapy versus nivolumab monotherapy in NSCLC patients.
We analyzed the FDA Adverse Event Reporting System (FAERS) database from 2004 Q1 to 2025 Q2. Disproportionality analysis using reporting odds ratio (ROR) and information component (IC) identified safety signals. Time-to-onset and clinical severity were compared between treatment groups.
Among 2,292 reports, combination therapy demonstrated significant disproportionality signals for glomerular-predominant renal injury, including glomerulonephritis minimal lesion (ROR = 78.62, IC025 = 2.096), nephrotic syndrome (ROR = 37.25, IC025 = 1.914), and glomerulosclerosis (ROR = 61.79, IC025 = 2.015). Pancreatic toxicity showed strong signals (ROR = 61.79, IC025 = 2.015). Additional renal signals included nephritis (ROR = 24.99, IC025 = 1.832) and renal failure (ROR = 2.99, IC025 = 0.499). Among 447 combination therapy reports, 39 renal events and 23 pancreatic events were identified, compared to 114 and 48 events respectively in 1,814 monotherapy reports. Median time-to-onset was 73 days for renal events and 84 days for pancreatic events in the combination group. Co-reported renal and pancreatic events were infrequent at the report level (2 of 60 combination therapy reports with renal and/or pancreatic events), and serious clinical outcomes including death and hospitalization were prevalent in both groups without statistically significant between-group differences.
Ipi+Nivo combination therapy is associated with prominent glomerular-predominant renal injury and pancreatic toxicity signals, potentially reflecting distinct immunological mechanisms whereby CTLA-4-dependent disruption of B-cell tolerance may predispose to glomerular injury while PD-1-mediated release of T-cell cytotoxicity may preferentially target pancreatic islets. These findings suggest the need for enhanced clinical vigilance and tailored monitoring strategies beyond conventional acute interstitial nephritis surveillance.

PMID:
42389519
Bibliographic data and abstract were imported from PubMed on 02 Jul 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.