Association between immune-related adverse events and recurrence dynamics under adjuvant anti-PD-1 therapy in resected melanoma.

Introduction: Adjuvant anti-PD-1 therapy has significantly improved recurrence-free survival (RFS) in patients with resected high-risk melanoma, yet a substantial proportion still relapse. Identifying predictors of recurrence remains a clinical priority. Methods: We retrospectively analyzed 84 patients with resected stage IIB-IV cutaneous melanoma who received adjuvant nivolumab or pembrolizumab. Clinicopathologic factors and immune-related adverse events (irAEs) occurring within the first 6 months of therapy were evaluated for their association with recurrence timing and RFS. Kaplan-Meier estimates, Cox regression models, and 3- and 6-month landmark analyses were used. Results: After a median follow-up of 30.7 months, 48.8% of patients experienced recurrence, including 25 patients who recurred during treatment. Recurrence during therapy was associated with advanced stage, greater Breslow thickness, and acral subtype. Cutaneous irAEs were significantly less frequent in patients who recurred during treatment (6.7% vs. 36.2%, p=0.010). In univariate Cox regression, cutaneous irAEs were associated with improved RFS (hazard ratio [HR]: 0.18; 95% CI: 0.04-0.73; p=0.017). This association remained significant in multivariate analysis (HR: 0.07; 95% CI: 0.01-0.56; p=0.011), independent of other clinicopathologic variables. Landmark analyses at 3 and 6 months confirmed the prognostic relevance of early cutaneous irAEs. Conclusions: Cutaneous irAEs within 6 months of initiating adjuvant PD-1 blockade are independently associated with reduced recurrence risk and prolonged RFS. Early emergence of these events may serve as a dynamic marker of effective anti-tumor immunity in patients with resected high-risk melanoma.