Immunotherapy Safety in Thymic Epithelial Tumors: A Disproportionality Analysis of the Food and Drug Administration Adverse Event Reporting System
ABSTRACT
Background:
Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, but their safety profile in patients with thymic epithelial tumors (TETs) remains poorly characterized due to the rarity of these malignancies.
Objective:
This study aims to comprehensively analyzed ICI-associated adverse events (irAEs) profiles in TETs patients using real-world pharmacovigilance data.
Methods:
We conducted a retrospective analysis of the FDA Adverse Event Reporting System (FAERS) database from the first quarter of 2016 through the fourth quarter of 2024. Cases of TETs with ICI-related AEs were identified and deduplicated following FDA recommendations. Disproportionality analysis was performed using reporting odds ratios (RORs) with the full FAERS database as a reference. Signals were defined as significant with at least 3 cases and a lower 95% confidence interval (CI) exceeded 1. Time-to-onset analysis and Weibull shape parameter testing were used to characterize the temporal pattern of irAEs. Clinical characteristics between fatal and non-fatal cases and cardiotoxicity specifics were analyzed descriptively.
Results:
Among 152 eligible TETs cases with irAEs, males slightly predominated (52.6%), with a median age of 58.5 years. Reports originated predominantly from the USA (33.6%) and Japan (10.5%). PD-1 inhibitors were implicated in 66.4% of cases. Disproportionality analysis identified 14 significant irAE signals across 11 System Organ Classes. Myositis (ROR 113.15, 95% CI 26.65-480.34), myocarditis (ROR 10.96, 95% CI 5.70-21.07), myasthenia gravis (ROR 3.86, 95% CI 1.86-7.85), and febrile neutropenia (ROR 18.33, 95% CI 4.57-73.55) demonstrated the strongest associations. The median time to irAE onset was 21.0 days, with 70% occurring within two months of treatment initiation. Fatal outcomes were reported in 23.7% (36/152) of cases, with a significantly higher proportion associated with PD-1 inhibitor use in the fatal group (80.0%) compared to the non-fatal group (61.6%, P<0.001). Myocarditis was the most frequent cardiotoxicity (51.3% of cardiac events).
Conclusions:
This large-scale pharmacovigilance study delineates a distinct and severe irAEs profile for ICIs in patients with TETs, characterized by robust disproportionality signals for myositis, cardiotoxicity, and myasthenia gravis. As a hypothesis-generating analysis, these findings underscore the need for vigilant monitoring and early detection strategies to mitigate irAEs risks, particularly in high-risk subgroups such as thymoma patients. The results provide clinically relevant evidence to guide risk-benefit evaluation and inform tailored surveillance protocols during ICI therapy in this population. Clinical Trial: Unnecessary
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