| アブストラクト | Immune checkpoint inhibitors (ICIs) have significantly improved outcomes in advanced malignancies but are frequently associated with immune-related adverse events. Vitiligo, a distinctive cutaneous immune-related adverse event, correlates with favorable prognosis in melanoma patients; however, its association with different ICI regimens and occurrence in nonmelanoma cancers remains inadequately characterized. We retrieved ICI-related vitiligo cases from the FDA Adverse Event Reporting System database between January 2015 and September 2025. Disproportionality analysis was performed using reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker algorithms. The potential biological mechanisms underlying vitiligo induced by ICIs were examined using The Cancer Genome Atlas data. A total of 591 ICI-induced vitiligo cases were identified, wherein 358 (60.6%) and 177 (29.9%) were reported as anti-programmed cell death protein 1 and combination therapy. Combination therapy exhibited the highest crude incidence rate (0.57%), while anti-programmed death-ligand 1 monotherapy showed the lowest (0.06%). The ipilimumab-pembrolizumab combination demonstrated the highest reporting odds ratio (97.2, 95% CI: 58.1-162.4). Median time-to-onset varied significantly across ICI classes: anti-cytotoxic T-lymphocyte-associated protein 4 monotherapy (33 days), anti-programmed death-ligand 1 (50 days), combination therapy (61 days), and anti-programmed cell death protein 1 (72 days). Patients aged 65 to 79 years showed significantly delayed onset. Geographic analysis revealed prolonged time-to-onset in Asian patients versus Americans. Pan-cancer transcriptomic analysis demonstrated correlations between ICI-induced vitiligo and melanocyte development, innate immunity, and mitochondrial function. ICI-induced vitiligo exhibits significant heterogeneity in risk across treatment strategies, with combination therapy and anti-cytotoxic T-lymphocyte-associated protein 4 strategies conferring higher relative risks. Onset timing is substantially influenced by age and geographic factors. Integration of pharmacovigilance and transcriptomic data implicates coordinated effects of melanocyte-lineage antigens, innate immune and mitochondrial function pathways in vitiligo pathogenesis. This study aimed to systematically characterize the risk profile, onset timing, and potential biological mechanisms of ICI-induced vitiligo across different treatment strategies and cancer types. |
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