A baseline systemic inflammatory signature predicts anti-PD-1 response in advanced melanoma

PURPOSE: Reliable baseline biomarkers to predict response to immune checkpoint inhibitors (ICI) in advanced melanoma remain limited. We evaluated whether pre-treatment circulating inflammatory, hematologic, and molecular markers could identify patients most likely to benefit from anti-PD-1 therapy. METHODS: In this retrospective cohort study, 136 patients with unresectable stage III or metastatic stage IV melanoma treated with anti-PD-1-based immunotherapy were analyzed. Baseline plasma cytokines were quantified by cytometric bead array, hematologic parameters were obtained from routine blood counts, and molecular features were extracted from clinical records. Multivariable logistic regression was used to identify independent predictors of treatment response, and model discrimination was assessed by receiver operating characteristic analysis. RESULTS: Responders exhibited lower IL-6 levels, higher IL-10 levels, a lower IL-6/IL-10 ratio, higher erythrocyte counts, lower monocyte counts, greater PD-L1 positivity, and more frequent BRAF V600 mutations. In multivariable analysis, elevated monocyte counts (OR 4.57, 95% CI 1.67-13.86) and increased IL-6 levels (OR 2.70, 95% CI 1.08-7.21) independently predicted non-response, whereas higher IL-10 levels (OR 0.16, 95% CI 0.04-0.51) and BRAF V600 mutations (OR 0.32, 95% CI 0.13-0.76) predicted favorable response. The multivariable model demonstrated good discriminatory performance (AUC 0.783), with 82% sensitivity and 72% specificity. CONCLUSIONS: Baseline systemic inflammatory and hematologic biomarkers independently predict anti-PD-1 response in advanced melanoma. IMPACT: Readily accessible blood-based biomarkers may support treatment stratification and improve selection of patients most likely to benefit from immunotherapy. Prospective validation in independent cohorts is warranted.