77155 From Survival to Side Effects: Retrospective Analysis of Adverse Events in Checkpoint Inhibitor Therapy for Melanoma Using the FAERS Database

Background Checkpoint inhibitors have significantly advanced melanoma treatment but are associated with a broad spectrum of adverse events (AEs), some of which are severe or fatal. Objective This study aimed to analyze AE patterns across PD‐1, PD‐L1, CTLA‐4, and LAG‐3 checkpoint inhibitors in melanoma, focusing on usage trends, AE severity, fatality reporting outcomes, and geographic distribution. Methods We conducted a retrospective study using data from the FDA Adverse Event Reporting System (FAERS) database, analyzing cases from January 2006 to December 2024. Descriptive statistics were used to evaluate AE severity, fatality reporting frequency, and geographic distribution. Additional analyses included combination therapy subgroup analyses, disproportionality analysis of selected immune‐related adverse events, multivariable logistic regression, and event‐to‐report lag analysis. Results PD‐1 inhibitors, especially pembrolizumab and nivolumab, had the highest number of reported cases and serious AEs (85.54% and 92.1%, respectively). Fatal outcomes were reported in 20.61% of pembrolizumab cases. However, FAERS data do not allow differentiation between deaths attributable to drug‐related toxicity versus underlying disease progression. Tremelimumab had the highest reports of fatality among CTLA‐4 inhibitors (53.66%). Relatlimab was associated with myocarditis. PD‐1 inhibitors and atezolizumab had a higher proportion of foreign cases. Combination therapy was associated with higher odds of serious AEs for nivolumab, ipilimumab, and relatlimab, while the foreign reporting region was frequently associated with higher odds of fatal outcomes. Limitations The study is subject to reporting biases, and although multivariable regression was used to adjust for available covariates, FAERS lacks detailed clinical information, including comorbidities, treatment duration, and disease severity. Conclusion Checkpoint inhibitors have transformed melanoma management but are associated with substantial immune‐related AEs. Our findings highlight the importance of dermatologic surveillance as an integral component of immunotherapy care. As immunotherapy use continues to expand, structured monitoring protocols and prompt dermatologic consultation should be considered standard components of melanoma management.