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Comparative Study
. 2025 May 2:220:115356.
doi: 10.1016/j.ejca.2025.115356. Epub 2025 Mar 15.

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

Sören Reinhard  1 , Jochen Sven Utikal  2 , Anne Zaremba  3 , Georg Lodde  3 , Imke von Wasielewski  4 , Kai Christian Klespe  4 , Friedegund Meier  5 , Sebastian Haferkamp  6 , Katharina C Kähler  7 , Rudolf Herbst  8 , Christoffer Gebhardt  9 , Anca Sindrilaru  10 , Edgar Dippel  11 , Yenny Angela  12 , Peter Mohr  13 , Claudia Pfoehler  14 , Andrea Forschner  15 , Martin Kaatz  16 , Beatrice Schell  17 , Anja Gesierich  18 , Carmen Loquai  19 , Jessica C Hassel  20 , Jens Ulrich  21 , Frank Meiss  22 , Gaston Schley  23 , Lucie M Heinzerling  24 , Michael Sachse  25 , Julia Welzel  26 , Carsten Weishaupt  27 , Cord Sunderkötter  28 , Christiane Michl  28 , Harm-Henning Lindhof  29 , Alexander Kreuter  30 , Markus V Heppt  31 , Saskia Wenk  32 , Cornelia Mauch  33 , Carola Berking  31 , Annekathrin Silvia Nedwed  34 , Ralf Gutzmer  12 , Ulrike Leiter  15 , Dirk Schadendorf  35 , Selma Ugurel  35 , Michael Weichenthal  7 , Maximilian Haist  1 , Maria Isabel Fleischer  1 , Berenice Lang  1 , Stephan Grabbe  1 , Henner Stege  36
Affiliations
Free article
Comparative Study

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

Sören Reinhard et al. Eur J Cancer. .
Free 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.

Keywords: Checkpoint inhibition; Melanoma; Response.

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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: SR, JSU, AZ, GL, IvW, KCK, FM, SH, RH, CG, AS, ED, YA, PM, AF, MK, BS, AG, GS, LMH, MS, CW, CS, CM, HHL, AK, SW, CMau, ASN, RG, UL, DS, MW, MH, MIF, BL, SG, HS declare no conflict of interest JCH received honoraria from BMS, Delcath, Immunocore, MSD, Novartis, Pierre Fabre, Sanofi and Sunpharma for talks and from Sunpharma for advisory board participation, travel support from BMS, Iovance and Sunpharma outside the submitted work. JU is on the advisory board or has received honoraria and travel support from Amgen, Bristol Myers Squibb, GSK, Immunocore, LeoPharma, Merck Sharp and Dohme, Novartis, Pierre Fabre, Rheacell, Roche and Sanofi outside the submitted work. MVH received honoraria from MSD, BMS, Roche, Novartis, Sun Pharma, Sanofi, Almirall, Biofrontera, Galderma, Immunocore, InfectoPharm. CB received speaker´s fees and/or honoraria for consultancy (advisory board) from BMS, Delcath, InflaRx, Immunocore, MSD, Novartis, Pierre Fabre, Regeneron, and Sanofi, outside the submitted work. FM served as consultant and/or has received honoraria from Novartis, Bristol-Myers Squibb, Merck Sharp & Dohme, Pierre Fabre, Sanofi Genzyme, Sun Pharma and travel support from Novartis, Sun Pharma, Roche, Pierre Fabre and Merck Sharp & Dohme, outside the submitted work. KCK served as consultant and/or has received honoraria from Bristol-Myers Squibb, Kyowa Kirin, Novartis, Recordati Rare Diseases, Vetter Pharma, Pierre Fabre, Sun Pharma SU declares research support from Bristol Myers Squibb and Merck Serono; speakers and advisory board honoraria from Bristol Myers Squibb, Merck Sharp & Dohme, Merck Serono, and Novartis; and meeting and travel support from Almirall, Bristol-Myers Squibb, IGEA Clinical Biophysics, Merck Sharp & Dohme, Novartis, Pierre Fabre, and Sun Pharma; outside the submitted work. CL declares speakers and advisory board honoraria from BMS, MSD, Merck, Roche, Immunocore, Novartis, Pierre Fabre, Sanofi, Sun Pharma, Almirall Hermal, Kyowa Kirin, Biontech, Boehriner Ingelheim, Merck, Roche, Almirall Hermal, Kyowa Kirin, Biontech, Lilly and travel support from BMS, MSD, Merck, Roche, Immunocore, Novartis, Pierre Fabre, Sanofi, Sun Pharma, Almirall Hermal, Kyowa Kirin, Biontech, Pfizer outside the submitted work. CP declares speakers, advisory board honoraria and travel support from MSD, BMS, Roche, Novartis, AbbVie, Sanofi, Merck Serono, Sun Pharma, Pierre Fabre, LEO, AMGEN and Allery Therapeutics outside the submitted work. JW received speaker fees and travel expenses support from BMS, MSD, Almirall, Abbvie, Sanofi, Leo Pharma, Novartis, Janssen, Boehringer Ingelheim and Lilly.

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