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

Sarah K Jacques; Janet McKeown; Piyush Grover; Douglas B Johnson; Anne Zaremba; Florentia Dimitriou; Roi Weiser; Mohamad Farid; Kenjiro Namikawa; Ryan J Sullivan; Piotr Rutkowski; Celeste Lebbe; Omid Hamid; Jonathan S Zager; Olivier Michielin; Bart Neyns; Yasuhiro Nakamura; Caroline Robert; Janice Mehnert; Paolo A Ascierto; Prachi Bhave; Benjamin Park; Lisa Zimmer; Joanna Mangana; Megan Mooradian; Joanna Placzke; Clare Allayous; Isabella C Glitza Oliva; Inderjit Mehmi; Danielle Depalo; Alexandre Wicky; Julia K Schwarze; Severine Roy; Christina Boatwright; Vito Vanella; Georgina V Long; Alexander M Menzies; Serigne N Lo; Matteo S Carlino

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

Eur J Cancer. 2024 Mar:199:113563. doi: 10.1016/j.ejca.2024.113563. Epub 2024 Jan 22.

Authors

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

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.

MeSH terms

Combined Modality Therapy
Humans
Melanoma* / drug therapy
Melanoma* / surgery
Neoplasm Recurrence, Local
Retrospective Studies
Skin Neoplasms* / drug therapy
Skin Neoplasms* / surgery

Grants and funding

P50 CA225450/CA/NCI NIH HHS/United States