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 if 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.

Real-World Outcomes of Inoperable and Metastatic Cutaneous Head and Neck Melanoma Patients.

OBJECTIVE: This study aims to describe the overall survival (OS) and to identify associated prognostic factors in patients with inoperable and metastatic cutaneous melanoma of the head and neck (H&N) region, undergoing modern systemic treatments. METHODS: This is a retrospective single institutional study. Data on all consecutive H&N melanoma patients treated with systemic oncologic treatments between 2015 and 2022 were collected from electronic medical files. Kaplan-Meier curves were used to describe survival and Cox regression analysis was used to identify patient and tumor factors associated with prognosis. RESULTS: A total of 144 patients were included. Median OS was 45 months (95% confidence interval [CI] 28-65 m). On univariable analysis for OS, the primary disease site, specifically the nape and neck (hazard ratio [HR] 3.3, 95% CI 1.4-7.7, p = 0.007), high Eastern Cooperative Oncology Group Performance Status ([ECOG-PS], HR 2.5, 95% CI = 1.9-3.3, p < 0.001), high lactate dehydrogenase (LDH) levels (HR 2.8, 95% CI = 1.7-4.6, p < 0.001), and treatment with targeted therapy (TT) as compared with immunotherapy (HR 2.6, 95% CI = 1.06-6.3, p = 0.03) were all associated with shorter OS. High-grade adverse events (AEs) were associated with a longer OS (HR 0.41, 95% CI = 0.25-0.68, p = 0.001). On multivariable analysis for OS, the ECOG-PS, LDH levels, site of disease, and the development of moderate-severe AEs remained significant. CONCLUSIONS: In the era of modern oncologic treatments, the prognosis of inoperable and metastatic cutaneous H&N melanoma aligns with other cutaneous melanomas. Primary tumor site of the nape and neck region emerges as a significant prognostic factor. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2762-2770, 2024.