Exploring the clinical significance of specific immune-related adverse events in melanoma patients undergoing immune checkpoint inhibitor therapy

Several studies have demonstrated that patients who experience immune-related adverse events (irAE) as a result of immunotherapy treatment, exhibit significantly improved outcomes compared to patients without toxicity. Data regarding the impact of specific irAE is, however, currently lacking. This is a real-world single-site cohort of 415 advanced melanoma patients who were treated with immunotherapy as first-line between 2014 and 2020, with a median follow-up of 24.5 months. The most frequent irAEs were cutaneous (classified as non-vitiligo, n = 110, 26.5% and vitiligo, n = 48, 11.6%), rheumatologic (n = 68, 16.4%), gastrointestinal (n = 66, 15.9%), endocrine (n = 61, 14.7%), and hepatitis (n = 50, 12%). Specific irAE that were significantly associated with survival benefit were rheumatologic (hazard ratio 0.34 for PFS, P < 0.001; hazard ratio 0.38 for OS, P < 0.001), non-vitiligo cutaneous (hazard ratio 0.58 for PFS, P < 0.001; hazard ratio 0.54 for OS, P = 0.001), vitiligo (hazard ratio 0.30 for PFS, P < 0.001; hazard ratio 0.29 for OS, P < 0.001), and endocrine (hazard ratio 0.6 for PFS, P = 0.01; hazard ratio 0.52 for OS, P < 0.001). Other types of irAEs, such as colitis, hepatitis and others - do not present this correlation. The occurrence of these specific irAEs may reflect a hyperactivated immune response and thus can serve as meaningful clinical biomarkers.