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Background: Anti-PD1-based immunotherapy is currently used in most patients with advanced melanoma. Despite the remarkable data regarding overall survival, the optimal treatment duration is still unknown., Methods: We evaluated the outcome of 125 patients with advanced melanoma with and without brain metastases (MBM), treated either with anti-PD1 monotherapy (N = 97) or combined with anti-CTLA4 (N = 28) after elective treatment discontinuation due to complete response (CR) (group A, N = 86), or treatment-limiting toxicity (N = 33) and investigator's decision (ID, N = 6) (group B) with subsequent CR., Results: For group A, median duration of treatment (mDoT) was 22 months (range 5-49) and median time to CR 9 months (range 2-47). Accordingly, mDoT for group B was 3 months (range 0-36) and median time to CR 7 months (range 1-32). Seven patients from group A and three from group B experienced disease recurrence. Off-treatment survival was not reached. Median off-treatment response time (mOTRt) was 19 months (range 0-42) and 25 months (range 0-66), respectively. For MBM, mOTRt was 17 months (range 7-41) and 28 months (range 9-39), respectively. After a median follow-up of 38 months (range 9-70), seven (5.6%) patients had deceased, one (0.8%) due to melanoma., Conclusions: Treatment discontinuation is feasible also in patients with MBM. Efficacy outcomes seemed to be similar in both groups of patients who achieved CR, regardless of reason for discontinuation. In patients who experienced disease relapse, treatment re-challenge with anti-PD1 resulted in subsequent renewed response., Competing Interests: Conflict of interest statement FD receives intermittent travel support from Pierre Fabre outside of the submitted work. AZ has received travel grants from Novartis and BMS outside of the submitted work. AC receives meeting, accommodation and travel support from Roche, Amgen and BMS. KCK serves as consultant to Roche, BMS, MSD and received travel grants and speaker fees from Roche, BMS, MSD, GSK, Amgen. LF reports grants from Novartis, grants from BMS, grants from MSD, outside the submitted work; FT received travel support from Novartis and Abbvie. LH receives fees for consultant/advisory role: Amgen, Bristol-Myers Squibb, Curevac, Roche Pharma, MSD Sharp & Dohme Sharp & Dohme, Novartis, Sanofi, Pierre Fabre. Research funding: Novartis. JH has intermittent project focused consultant or advisory relationships with Merck Sharp & Dohme, Pierre Fabre and Sunpharma and has received speaker honoraria from Novartis, BMS and travel support from Pierre Fabre and BMS outside of the submitted work. PAA has/had a consultant/advisory role for Bristol Myers Squibb, Roche-Genentech, Merck Sharp & Dohme, Array, Novartis, Merck Serono, Pierre Fabre, Incyte, NewLink Genetics, Genmab, Medimmune, AstraZeneca, Syndax, SunPharma, Sanofi, Idera, Ultimovacs, Sandoz, Immunocore, 4SC, Alkermes, Italfarmaco, Nektar, Boehringer-Ingelheim. He also received research funds from Bristol Myers Squibb, Roche-Genentech, Array and travel support from MSD. OM reports grants and personal fees from Bristol Myers Squibb (BMS), grants and personal fees from MSD, personal fees from Roche, outside the submitted work. AH received consultancy and speaker honoraria from the following companies: Amgen, BMS, MerckPfizer, MSD, Novartis, Philogen, Pierre Fabre, Provectus, Regeneron and Roche. CL received consultancy and speaker honoraria from the following companies: Amgen, BMS, MerckPfizer, MSD, Novartis, Pierre Fabre and Roche. EL served as consultant or/and has received honoraria from Amgen, Actelion, Roche, Bristol Myers Squibb (BMS), Merck Sharp & Dohme (MSD, Novartis, Janssen, Medac and travel support from Amgen, Merck Sharp & Dohme (MSD), Bristol Myers Squibb (BMS), Amgen, Pierre Fabre, Sunpharma and Novartis. ER reports personal fees from Amgen, personal fees from Sanofi, outside the submitted work. RD has intermittent, project focused consulting and/or advisory relationships with Novartis, Merck Sharp & Dohme (MSD), Bristol Myers Squibb (BMS), Roche, Amgen, Takeda, Pierre Fabre outside the submitted work. JM has intermittent project focused consultant or advisory relationships with Merck/Pfizer, Merck Sharp & Dohme, Amgen, Novartis and Pierre Fabre and has received travel support from Ultrasun, L’ oreal, Merck Sharp & Dohme, Bristol Myers and Squibb und Pierre Fabre outside of the submitted work. CG, SSch and PFC have declared no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)