The efficacy of immune checkpoint blockade for melanoma in-transit with or without nodal metastases – A multicenter cohort study

Carl Jacob Holmberg, Lars Ny, Tina J. Hieken, Matthew S. Block, Michael J. Carr, Vernon K. Sondak, Christoffer Örtenwall, Dimitrios Katsarelias, Florentia Dimitriou, Alexander M. Menzies, Robyn PM Saw, Aljosja Rogiers, Richard J. Straker, Giorgos Karakousis, Rona Applewaite, Lalit Pallan, Dale Han, John T. Vetto, David E. Gyorki, Emilia Nan TieMaria Grazia Vitale, Paulo A. Ascierto, Reinhard Dummer, Jade Cohen, Jane YC Hui, Jacob Schachter, Nethanel Asher, H. Helgadottir, Harvey Chai, Hidde Kroon, Brendon Coventry, Luke D. Rothermel, James Sun, Matteo S. Carlino, Zoey Duncan, Kristy Broman, Jeffrey Weber, Ann Y. Lee, Russell S. Berman, Jüri Teras, David W. Ollila, Georgina V. Long, Jonathan S. Zager, Alexander van Akkooi, Roger Olofsson Bagge

Research output: Contribution to journalArticlepeer-review


Purpose: Guidelines addressing melanoma in-transit metastasis (ITM) recommend immune checkpoint inhibitors (ICI) as a first-line treatment option, despite the fact that there are no efficacy data available from prospective trials for exclusively ITM disease. The study aims to analyze the outcome of patients with ITM treated with ICI based on data from a large cohort of patients treated at international referral clinics. Methods: A multicenter retrospective cohort study of patients treated between January 2015 and December 2020 from Australia, Europe, and the USA, evaluating treatment with ICI for ITM with or without nodal involvement (AJCC8 N1c, N2c, and N3c) and without distant disease (M0). Treatment was with PD-1 inhibitor (nivolumab or pembrolizumab) and/or CTLA-4 inhibitor (ipilimumab). The response was evaluated according to the RECIST criteria modified for cutaneous lesions. Results: A total of 287 patients from 21 institutions in eight countries were included. Immunotherapy was first-line treatment in 64 (22%) patients. PD-1 or CTLA-4 inhibitor monotherapy was given in 233 (81%) and 23 (8%) patients, respectively, while 31 (11%) received both in combination. The overall response rate was 56%, complete response (CR) rate was 36%, and progressive disease (PD) rate was 32%. Median PFS was ten months (95% CI 7.4–12.6 months) with a one-, two-, and five-year PFS rate of 48%, 33%, and 18%, respectively. Median MSS was not reached, and the one-, two-, and five-year MSS rates were 95%, 83%, and 71%, respectively. Conclusion: Systemic immunotherapy is an effective treatment for melanoma ITM. Future studies should evaluate the role of systemic immunotherapy in the context of multimodality therapy, including locoregional treatments such as surgery, intralesional therapy, and regional therapies.

Original languageEnglish (US)
Pages (from-to)210-222
Number of pages13
JournalEuropean Journal of Cancer
StatePublished - Jul 2022


  • Immune checkpoint inhibitor
  • In-transit metastasis
  • Ipilimumab
  • Melanoma
  • Nivolumab
  • PD-1
  • Pembrolizumab

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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