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

Year: 2025

Type: article

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.

Source: European Journal of Cancer

DOI: 10.1016/j.ejca.2025.115356

Institutions: University Medical Center of the Johannes Gutenberg University Mainz, German Cancer Research Center, Heidelberg University, University Medical Centre Mannheim, Essen University Hospital, Deutsches Konsortium für Translationale Krebsforschung, Medizinische Hochschule Hannover, University Hospital Carl Gustav Carus, University Hospital Regensburg, University Hospital Schleswig-Holstein, Helios Klinikum Erfurt, University Medical Center Hamburg-Eppendorf, University Hospital Ulm, Klinikum Ludwigshafen, Johannes Wesling Klinikum Minden, Ruhr University Bochum, Elbe Kliniken Stade-Buxtehude, Universitätsklinikum des Saarlandes, Saarland University, University of Tübingen, German Red Cross, SRH Wald-Klinikum Gera, Universitätsklinikum Würzburg, University Hospital Heidelberg, National Center for Tumor Diseases, University of Freiburg, University Medical Center Freiburg, Helios Hospital Schwerin, Ludwig-Maximilians-Universität München, Klinikum Bremerhaven-Reinkenheide, University Hospital Augsburg, University of Münster, University Hospital Münster, Martin Luther University Halle-Wittenberg, Düsseldorf University Hospital, Witten/Herdecke University, HELIOS St. Elisabeth Klinik Oberhausen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Comprehensive Cancer Center Erlangen, Goethe University Frankfurt, Klinikum Darmstadt

Language: English

Topic: Cancer Immunotherapy and Biomarkers

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,270

Funders: Amgen, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, Sanofi, Regeneron Pharmaceuticals, Les Laboratories Pierre Fabre, Recordati Rare Diseases, Galderma, Sun Pharma, InflaRx, LEO Pharma, Sanofi Genzyme

OpenAlex ID: W4408479090