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

BackgroundIpilimumab 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.MethodsWe 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.ResultsAmong 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.