First-line checkpoint inhibitor therapy in metastatic acral lentiginous melanoma compared to other types of cutaneous melanoma: A multicenter study from the prospective skin cancer registry ADOREG

Reinhard S, Utikal JS, Zaremba A, Lodde G, von Wasielewski I, Klespe KC, Meier F, Haferkamp S, Kähler KC, Herbst R, Gebhardt C, Sindrilaru A, Dippel E, Angela Y, Mohr P, Pfoehler C, Forschner A, Kaatz M, Schell B, Gesierich A, Loquai C, Hassel JC, Ulrich J, Meiss F, Schley G, Heinzerling LM, Sachse M, Welzel J, Weishaupt C, Sunderkötter C, Michl C, Lindhof HH, Kreuter A, Heppt M, Wenk S, Mauch C, Berking C, Nedwed AS, Gutzmer R, Leiter U, Schadendorf D, Ugurel S, Weichenthal M, Haist M, Fleischer MI, Lang B, Grabbe S, Stege H (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Book Volume: 220

Article Number: 115356

DOI: 10.1016/j.ejca.2025.115356

Abstract

Background: Melanoma is the main cause of skin cancer-related death. Treatment with immune checkpoint inhibitors (CPI) has improved the prognosis in recent years. However, subtypes of melanoma differ in their response. Acral lentiginous melanoma (ALM) has a worse prognosis compared to cutaneous melanoma other than ALM (CM) and is therefore of particular relevance. Aims: To evaluate the efficacy of CPI in first-line treatment of patients with advanced ALM compared CM. Methods: Retrospective analysis of patients with metastatic ALM (n = 45) or CM (n = 328) who received first-line CPI therapy from the multicenter prospective skin cancer registry ADOREG. Study endpoints were best overall response (BOR), progression-free survival (PFS) and overall survival (OS). Results: ALM patients had significantly higher rates of ulcerated tumors, loco regional metastases and fewer BRAF-mutated tumors compared to CM patients. Combined CPI was administered in 48.9 % ALM patients and 39.3 % of CM patients, while the remaining patients received PD-1 monotherapy. OS trended to be shorter in patients with ALM (18.1 vs. 43.8 months, p = 0.10) with no significant differences in PFS (7.0 vs. 11.5 months, p = 0.21). In patients with CM, median OS with combined CPI was not reached, whereas the median OS after PD-1 monotherapy was 37.8 months (p = 0.22). Conversely, in patients with ALM, OS with combined CPI was 17.8 months, compared to 26 months with PD-1 monotherapy (p = 0.15). There were no significant differences in BOR between patients with ALM or CM. Conclusion: Analysis of this real-world cohort of patients with metastatic melanoma showed a trend towards poorer survival outcomes upon first-line treatment with CPI in ALM compared to cutaneous melanoma of other subtypes.

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Involved external institutions

Universitätsmedizin der Johannes Gutenberg-Universität Mainz Germany (DE) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Universitätsklinikum Carl Gustav Carus Dresden Germany (DE) Universitätsklinikum Regensburg Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) Germany (DE) HELIOS Kliniken Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Universitätsklinikum Ulm Germany (DE) Klinikum der Stadt Ludwigshafen am Rhein gGmbH Germany (DE) Ruhr-Universität Bochum (RUB) Germany (DE) Elbe Kliniken Stade-Buxtehude Germany (DE) Universitätsklinikum des Saarlandes (UKS) Germany (DE) Eberhard Karls Universität Tübingen Germany (DE) DRK Krankenhaus Chemnitz-Rabenstein Germany (DE) SRH Wald-Klinikum Gera Germany (DE) Universitätsklinikum Würzburg Germany (DE) Klinikum Bremen-Ost Germany (DE) Universitätsklinikum Heidelberg Germany (DE) Harzklinikum Dorothea Christiane Erxleben Germany (DE) Universitätsklinikum Freiburg Germany (DE) Klinikum der Universität München (LMU Klinikum) Germany (DE) Klinikum Bremerhaven-Reinkenheide Germany (DE) Universitätsklinikum Augsburg Germany (DE) Universitätsklinikum Münster Germany (DE) Martin-Luther-Universität Halle-Wittenberg (MLU) Germany (DE) Universitätsklinikum Düsseldorf Germany (DE) Universität Witten/Herdecke Germany (DE) Goethe-Universität Frankfurt am Main Germany (DE) Universitätsklinikum Mannheim / University Medical Centre Mannheim (Universitätsmedizin Mannheim) Germany (DE)

How to cite

APA:

Reinhard, S., Utikal, J.S., Zaremba, A., Lodde, G., von Wasielewski, I., Klespe, K.C.,... Stege, H. (2025). First-line checkpoint inhibitor therapy in metastatic acral lentiginous melanoma compared to other types of cutaneous melanoma: A multicenter study from the prospective skin cancer registry ADOREG. European Journal of Cancer, 220. https://doi.org/10.1016/j.ejca.2025.115356

MLA:

Reinhard, Sören, et al. "First-line checkpoint inhibitor therapy in metastatic acral lentiginous melanoma compared to other types of cutaneous melanoma: A multicenter study from the prospective skin cancer registry ADOREG." European Journal of Cancer 220 (2025).

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