Outcomes of patients with resected stage III/IV acral or mucosal melanoma, treated with adjuvant anti-PD-1 based therapy

Sarah K Jacques¹, Janet McKeown², Piyush Grover², Douglas B Johnson³, Anne Zaremba⁴, Florentia Dimitriou⁵, Roi Weiser⁶, Mohamad Farid⁷, Kenjiro Namikawa⁸, Ryan J Sullivan⁹, Piotr Rutkowski¹⁰, Celeste Lebbe¹¹, Omid Hamid¹², Jonathan S Zager¹³, Olivier Michielin¹⁴, Bart Neyns¹⁵, Yasuhiro Nakamura¹⁶, Caroline Robert¹⁷, Janice Mehnert¹⁸, Paolo A Ascierto¹⁹, Prachi Bhave²⁰, Benjamin Park³, Lisa Zimmer⁴, Joanna Mangana⁵, Megan Mooradian⁹, Joanna Placzke¹⁰, Clare Allayous¹¹, Isabella C Glitza Oliva⁶, Inderjit Mehmi¹², Danielle Depalo¹³, Alexandre Wicky¹⁴, Julia K Schwarze¹⁵, Severine Roy¹⁷, Christina Boatwright¹⁸, Vito Vanella¹⁹, Georgina V Long²¹, Alexander M Menzies²², Serigne N Lo²³, Matteo S Carlino²⁴

Affiliations

¹ Department of Medical Oncology, Westmead and Blacktown Hospitals, Sydney, Australia.
² Melanoma Institute Australia, The University of Sydney, Sydney, Australia.
³ Vanderbilt University Medical Centre, Nashville, TN, USA.
⁴ Department of Dermatology, Venereology and Allergology, University Hospital Essen, Essen, Germany.
⁵ Department of Dermatology, University Hospital of Zurich and Faculty of Medicine, University of Zürich, Zurich, Switzerland.
⁶ MD Anderson Cancer Center, Houston, TX, USA.
⁷ National Cancer Centre, Singapore.
⁸ Department of Dermatologic Oncology, National Cancer Center, Tokyo, Japan.
⁹ Massachusetts General Hospital, Harvard University, Boston, MA, USA.
¹⁰ Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
¹¹ Université Paris Cite,AP-HP Dermato-oncology, Cancer institute APHP.nord Paris cité, INSERM U976, Saint Louis Hospital, Paris, France.
¹² The Angeles Clinic, A Cedars-Sinai Affiliate, Los Angeles, CA, USA.
¹³ Department of Cutaneous Oncology, Moffit Cancer Center, Tampa, FL, USA.
¹⁴ Department of Oncology, Lausanne University Hospital, Lausanne, Switzerland.
¹⁵ Universitair Ziekenhuis Brussel, Brussels, Belgium.
¹⁶ Department of Skin Oncology/Dermatology, Comprehensive Cancer Center, Saitama Medical University International Medical Center, Saitama, Japan.
¹⁷ Institute Gustave Roussy and Paris Saclay University, Villejuif Cedex, France.
¹⁸ NYU Langone, New York City, NY, USA.
¹⁹ Istituto Nazionale Tumori IRCCS Fondazione Pascale, Napoli, Italy.
²⁰ Sir Peter MacCallum Cancer Centre Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia.
²¹ Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia; Royal North Shore Hospital, Sydney, Australia.
²² Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia; Royal North Shore Hospital, Sydney, Australia; Mater Hospital, Sydney, Australia.
²³ Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
²⁴ Department of Medical Oncology, Westmead and Blacktown Hospitals, Sydney, Australia; Melanoma Institute Australia, The University of Sydney, Sydney, Australia. Electronic address: matteo.carlino@sydney.edu.au.

PMID: 38278007
DOI: 10.1016/j.ejca.2024.113563

Outcomes of patients with resected stage III/IV acral or mucosal melanoma, treated with adjuvant anti-PD-1 based therapy

Sarah K Jacques et al. Eur J Cancer. 2024 Mar.

. 2024 Mar:199:113563.

doi: 10.1016/j.ejca.2024.113563. Epub 2024 Jan 22.

Authors

Affiliations

¹ Department of Medical Oncology, Westmead and Blacktown Hospitals, Sydney, Australia.
² Melanoma Institute Australia, The University of Sydney, Sydney, Australia.
³ Vanderbilt University Medical Centre, Nashville, TN, USA.
⁴ Department of Dermatology, Venereology and Allergology, University Hospital Essen, Essen, Germany.
⁵ Department of Dermatology, University Hospital of Zurich and Faculty of Medicine, University of Zürich, Zurich, Switzerland.
⁶ MD Anderson Cancer Center, Houston, TX, USA.
⁷ National Cancer Centre, Singapore.
⁸ Department of Dermatologic Oncology, National Cancer Center, Tokyo, Japan.
⁹ Massachusetts General Hospital, Harvard University, Boston, MA, USA.
¹⁰ Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
¹¹ Université Paris Cite,AP-HP Dermato-oncology, Cancer institute APHP.nord Paris cité, INSERM U976, Saint Louis Hospital, Paris, France.
¹² The Angeles Clinic, A Cedars-Sinai Affiliate, Los Angeles, CA, USA.
¹³ Department of Cutaneous Oncology, Moffit Cancer Center, Tampa, FL, USA.
¹⁴ Department of Oncology, Lausanne University Hospital, Lausanne, Switzerland.
¹⁵ Universitair Ziekenhuis Brussel, Brussels, Belgium.
¹⁶ Department of Skin Oncology/Dermatology, Comprehensive Cancer Center, Saitama Medical University International Medical Center, Saitama, Japan.
¹⁷ Institute Gustave Roussy and Paris Saclay University, Villejuif Cedex, France.
¹⁸ NYU Langone, New York City, NY, USA.
¹⁹ Istituto Nazionale Tumori IRCCS Fondazione Pascale, Napoli, Italy.
²⁰ Sir Peter MacCallum Cancer Centre Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia.
²¹ Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia; Royal North Shore Hospital, Sydney, Australia.
²² Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia; Royal North Shore Hospital, Sydney, Australia; Mater Hospital, Sydney, Australia.
²³ Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
²⁴ Department of Medical Oncology, Westmead and Blacktown Hospitals, Sydney, Australia; Melanoma Institute Australia, The University of Sydney, Sydney, Australia. Electronic address: matteo.carlino@sydney.edu.au.

PMID: 38278007
DOI: 10.1016/j.ejca.2024.113563

Abstract

Importance: Acral (AM) and mucosal melanomas (MM) are rare subtypes with a poor prognosis. In those with advanced disease, anti-PD-1 (PD1) therapy has reduced activity compared to that seen in non-acral cutaneous melanoma.

Objective: To determine the efficacy of adjuvant PD1 in resected AM or MM.

Design: An international, retrospective cohort study SETTING: Data up to November 2021 collected from 20 centres across 10 countries.

Participants: One hundred and ninety four patients with resected stage III or IV¹ AM or MM who received adjuvant PD1 were included and compared to matched patients from the Melanoma Institute Australia (MIA) database using a propensity score matching analysis.

Main outcomes and measures: Recurrence-free survival (RFS), distant metastasis-free survival (DMFS) and overall survival (OS) were investigated.

Results: Forty five of 139 (32%) AM and 9 of 55 (16%) MM patients completed adjuvant therapy. The main reason for early treatment cessation in both groups was disease recurrence: 51 (37%) and 30 (55%) in the AM and MM groups, respectively. In the AM group adjuvant PD1 was associated with a longer RFS [HR-0.69 (0.52-0.92, p = 0.0127)], DMFS [HR0.58 (0.38-0.89, p = 0.0134)] and OS [HR of 0.59 (0.38-0.92, p-value 0.0196)] when compared to the historical cohort. In the MM group there was no statistical difference in RFS [HR1.36 (0.69-2.68,p-value 0.3799], DMFS or OS.

Conclusion and relevance: After adjuvant PD1, both AM and MM have a high risk of recurrence. Our data suggests a benefit to using adjuvant PD1 therapy in resected AM but not in resected MM. Additional studies to investigate the efficacy of adjuvant PD1 for MM are needed.

Keywords: Acral melanoma; Adjuvant; Anti-PD1; Immunotherapy; Mucosal melanoma.

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Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MSC: consultant advisor for Amgen, BMS, Eisai, Ideaya, MSD, Nektar, Novartis, Oncosec, Pierre-Fabre, Qbiotics, Regeneron, Roche, Merck and Sanofi, and received honoraria from BMS, MSD, Sanofi and Novartis. DBJ: advisory boards or as a consultant for BMS, Catalyst Biopharma, Iovance, Mallinckrodt, Merck, Mosaic ImmunoEngineering, Novartis, Oncosec, Pfizer, Targovax, and Teiko, and has received research funding from BMS and Incyte. RJS: Advisory boards/consulting for BMS, Merck, Novartis, Marengo, Pfizer, and Replimune and received research funding from Merck. FD: receives/received honoraria and travel support from Pierre Fabre, Merck Sharp & Dohme, Bristol Myers Squibb and Sun Pharma.CL : consultant advisor for BMS, MSD, Novartis, Pierre-Fabre, Merck and Sanofi YN: advisory boards/consulting for MSD and Novartis and received honoraria from Alexion Pharma, BMS, Maruho, MSD, Novartis, Ono Pharma, Sanofi, SunPharma, and Tanabe-Mitsubishi Pharma AMM: consultant advisor for BMS, MSD, Novartis, Roche, Pierre-Fabre, QBioticsKN: advisory board for Novartis and MSD, honoraria from Ono pharmaceutical, Novartis, Bristol-Myers Squibb, and MSD.LZ: served as consultant and has received honoraria from BMS, MSD, Novartis, Pierre Fabre, Sanofi, and Sunpharma and travel support from MSD, BMS, Pierre Fabre, Sanofi, Sunpharma and Novartis, outside the submitted work.JS: Honoraria: Novartis; Travel, Accommodations, Expenses: Amgen, Merck Sharp & DohmePB: conference sponsorship BMS, MSD, Novartis; speaker fees: Novartis, MSD.JP: Received travel support from Pierre Fabre, MSD, BMS, Novartis outside the scope of this study. All remaining authors have declared no conflicts of interest.

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Outcomes of patients with resected stage III/IV acral or mucosal melanoma, treated with adjuvant anti-PD-1 based therapy

Affiliations

Outcomes of patients with resected stage III/IV acral or mucosal melanoma, treated with adjuvant anti-PD-1 based therapy

Authors

Affiliations

Abstract

Conflict of interest statement

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical