Objective:

To characterize severe renal and pancreatic toxicities associated with ipilimumab plus nivolumab (Ipi+Nivo) combination therapy versus nivolumab monotherapy in NSCLC patients, specifically focusing on the differences in adverse events.

Key Findings:

• Combination therapy showed significant disproportionality signals for glomerular-predominant renal injury and pancreatic toxicity, based on analysis of 2,292 reports.
• Notable renal events included glomerulonephritis minimal lesion (ROR = 78.62), nephrotic syndrome (ROR = 37.25), and glomerulosclerosis (ROR = 61.79).
• Pancreatic toxicity also showed strong signals (ROR = 61.79).
• Median time-to-onset for renal events was 73 days and for pancreatic events was 84 days in the combination group.
• Co-reported renal and pancreatic events were infrequent, with serious outcomes prevalent in both treatment groups.

Interpretation:

The findings suggest distinct immunological mechanisms may predispose patients to specific organ injuries associated with Ipi+Nivo therapy, highlighting the need for tailored monitoring.

Limitations:

• The study relies on spontaneous reporting, which may lead to underreporting or overreporting of adverse events, potentially skewing the findings.
• Data may not capture all relevant clinical information or outcomes due to the nature of the FAERS database.

Conclusion:

Enhanced clinical vigilance and tailored monitoring strategies are suggested for patients receiving Ipi+Nivo therapy due to the identified renal and pancreatic toxicities, emphasizing the need for proactive management.