Comparative safety of nivolumab plus ipilimumab versus nivolumab plus relatlimab in advanced melanoma: a real-world pharmacovigilance study

Background Nivolumab plus ipilimumab (NIVO-IPI) and nivolumab plus relatlimab (NIVO-RELA) were approved for treating advanced melanoma. There is no real-world insights into differential adverse eventm (AE) risks across two regimens. Methods We conducted a disproportionality analysis using the FDA Adverse Event Reporting System (FAERS) database for NIVO-IPI and NIVO-RELA from the fouth quarter (Q4) of 2015 to 2024Q4 by calculating the reporting odds ratios (ROR) and information component (IC) with 95% confidence intervals (ICs). Results In total, 7482 and 185 records were extracted to analyze from FAERS for NIVO-IPI and NIVO-RELA, respectively. NIVO-IPI showed higher significant risks in gastrointestinal (ROR = 1.39), endocrine (ROR = 3.10), hepatobiliary (ROR = 2.32), metabolism and nutrition (ROR = 1.44), and respiratory, thoracic and mediastinal disorders (ROR = 1.18), especially in preferred terms (PTs) of colitis, hypophysitis, pneumonia and hepatitis. NIVO-RELA had elevated risks in cardiac (ROR = 2.84) and vascular disorders (ROR = 2.04), especially in PTs of myocarditis, troponin elevation, and myasthenia gravis. 80% of AEs occurred within 3 months for both regimens. Median time-to-onset was 42 days (NIVO-IPI) vs. 57 days (NIVO-RELA), with no statistical difference ( p  = 0.66). Conclusion NIVO-IPI was associated with broader immune-related toxicities, while NIVO-RELA exhibited higher cardiac-specific risks. These findings underscore the need for tailored AE monitoring based on treatment selection.