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Anti-programmed death-1 (anti-PD1) treatment has significantly improved outcomes of advanced melanoma with a considerable percentage of patients achieving complete response (CR). This real-world study analyzed the feasibility of elective anti-PD1 discontinuation in advanced melanoma patients with CR and evaluated factors related to sustained response. Thirty-five patients with advanced cutaneous or primary unknown melanoma with CR to nivolumab or pembrolizumab from 11 centers were included. Mean age was 66.5 years, and 97.1% had ECOG PS 0-1. 28.6% had ≥3 metastatic sites with 58.8% having M1a-M1b disease; 8.6% had liver and 5.7% had brain metastases. At baseline, 80% had normal LDH, and 85.7% had a neutrophil-to-lymphocyte ratio ≤3. 74.3% of patients had CR confirmed in PET-CT. Median duration of anti-PD1 was 23.4 months (range 1.3-50.5). 24 months after therapy discontinuation, 91.9% of patients were progression-free. Estimated PFS and OS at 36, 48, and 60 months from the start of anti-PD1 were 94.2%, 89.9%, 84.3%, and 97.1%, 93.3%, 93.3%, respectively. Antibiotics use after anti-PD1 discontinuation increased the odds of progression (OR 16.53 [95% CI 1.7, 226.03]). The study confirms the feasibility of elective anti-PD1 discontinuation in advanced melanoma patients with CR and favorable prognostic factors at baseline., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)