Response to immune checkpoint inhibitors in acral melanoma: A nationwide cohort study

Olivier J van Not, Melissa M de Meza, Alfons J M van den Eertwegh, John B Haanen, Christian U Blank, Maureen J B Aarts, Franchette W P J van den Berkmortel, Jesper van Breeschoten, Jan-Willem B de Groot, Geke A P Hospers, Rawa K Ismail, Ellen Kapiteijn, Djura Piersma, Roos S van Rijn, Marion A M Stevense-den Boer, Astrid A M van der Veldt, Gerard Vreugdenhil, Han J Bonenkamp, Marye J Boers-Sonderen, Willeke A M BlokxMichel W J M Wouters, Karijn P M Suijkerbuijk

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Background: Recent reports suggest the limited efficacy of immune checkpoints inhibitors in advanced acral melanoma (AM). This study aims to investigate the clinical outcomes of immune checkpoint inhibitors in patients with stage III and IV AM and compare them to cutaneous melanoma (CM). Methods: We included patients with advanced AM and CM treated with first-line anti-programmed cell death (PD)-1 monotherapy or ipilimumab-nivolumab registered in the prospective nationwide Dutch Melanoma Treatment Registry. Objective response rates, progression-free survival (PFS) and overall survival (OS) were calculated. A Cox proportional hazard model was used to assess the prognostic factors with PFS and OS. Results: In total, 2058 patients (88 AM and 1970 CM) with advanced melanoma were included. First-line objective response rates were 34% for AM versus 54% for CM in the advanced anti-PD-1 cohort and 33% for AM versus 53% for CM in the advanced ipilimumab-nivolumab cohort. The Median PFS was significantly shorter for anti-PD-1 treated AM patients (3.1 months; 95%CI: 2.8–5.6) than patients with CM (10.1 months; 95%CI: 8.5–12.2) (P < 0.001). In patients with advanced melanoma, AM was significantly associated with a higher risk of progression (HRadj 1.63; 95%CI: 1.26–2.11; P < 0.001) and death (HRadj 1.54; 95%CI: 1.15–2.06; P = 0.004) than CM. Conclusions: This study shows lower effectiveness of anti-PD -1 monotherapy and ipilimumab-nivolumab in AM, with lower response rates, PFS and OS than CM. This group of patients should be prioritised in the development of alternative treatment strategies.

Original languageEnglish
Pages (from-to)70-80
Number of pages11
JournalEuropean journal of cancer (Oxford, England : 1990)
Publication statusPublished - May 2022

Bibliographical note

Funding Information:
For the Dutch Melanoma Treatment Registry (DMTR), the Dutch Institute for Clinical Auditing foundation received a start-up grant from governmental organisation, The Netherlands Organisation for Health Research and Development (ZonMW, project number 836002002). The DMTR is structurally funded by Bristol-Myers Squibb, Merck Sharpe & Dohme, Novartis, and Roche Pharma. Roche Pharma stopped funding in 2019, and Pierre Fabre started funding the DMTR in 2019. For this work, no funding was granted.

Funding Information:
CB has received commercial research grants from Novartis, BristolMyers Squibb, and NanoString; is a paid advisory board member for Bristol Myers Squibb, MSD, Roche, Novartis, GlaxoSmithKline, AstraZeneca, Pfizer, Lilly, GenMab, and Pierre Fabre; and holds ownership interest in Uniti Cars, Neon Therapeutics, and Forty Seven.

Publisher Copyright:
© 2022 The Author(s)


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