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.
S��ren Reinhard, Jochen Sven Utikal, Anne Zaremba, Georg Lodde, Imke von Wasielewski, Kai Christian Klespe, Friedegund Meier, Sebastian Haferkamp, Katharina C K��hler, Rudolf Herbst, Christoffer Gebhardt, Anca Sindrilaru, Edgar Dippel, Yenny Angela, Peter Mohr, Claudia Pfoehler, Andrea Forschner, Martin Kaatz, Beatrice Schell, Anja Gesierich, Carmen Loquai, Jessica C Hassel, Jens Ulrich, Frank Meiss, Gaston Schley, Lucie M Heinzerling, Michael Sachse, Julia Welzel, Carsten Weishaupt, Cord Sunderk��tter, Christiane Michl, Harm-Henning Lindhof, Alexander Kreuter, Markus V Heppt, Saskia Wenk, Cornelia Mauch, Carola Berking, Annekathrin Silvia Nedwed, Ralf Gutzmer, Ulrike Leiter, Dirk Schadendorf, Selma Ugurel, Michael Weichenthal, Maximilian Haist, Maria Isabel Fleischer, Berenice Lang, Stephan Grabbe, Henner Stege
Author Information
S��ren Reinhard: Department of Dermatology, University Medical Center Mainz, Mainz 55131, Germany.
Jochen Sven Utikal: Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany.
Anne Zaremba: Department of Dermatology, Venereology and Allergology, University Hospital Essen and German Cancer Consortium (DKTK), Partner Site Essen/D��sseldorf, Essen, Germany.
Georg Lodde: Department of Dermatology, Venereology and Allergology, University Hospital Essen and German Cancer Consortium (DKTK), Partner Site Essen/D��sseldorf, Essen, Germany.
Imke von Wasielewski: Skin Cancer Center Hannover, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany.
Kai Christian Klespe: Skin Cancer Center Hannover, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany.
Friedegund Meier: Department of Dermatology, University Hospital Carl Gustav Carus, Dresden, Germany.
Sebastian Haferkamp: Department of Dermatology, University Hospital Regensburg, Regensburg, Germany.
Katharina C K��hler: Department of Dermatology, Skin Cancer Center, University Hospital Schleswig-Holstein - Campus Kiel, Kiel, Germany.
Rudolf Herbst: Department of Dermatology, HELIOS Hospital Erfurt, Erfurt, Germany.
Christoffer Gebhardt: Department of Dermatology and Venerology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Anca Sindrilaru: Department of Dermatology, University Hospital of Ulm, Ulm, Germany.
Edgar Dippel: Department of Dermatology, Ludwigshafen City Hospital, Ludwigshafen, Germany.
Yenny Angela: Department of Dermatology, Muehlenkreiskliniken Minden and Ruhr University Bochum, Minden, Germany.
Peter Mohr: Department of Dermatology, Elbe Kliniken Buxtehude, Buxtehude, Germany.
Claudia Pfoehler: Department of Dermatology, Saarland University Hospital and Saarland University Faculty of Medicine, Homburg, Germany.
Andrea Forschner: Center for Dermatooncology, Department of Dermatology, Eberhard-Karls University of T��bingen, Tubingen, Germany.
Martin Kaatz: Department of Dermatology, DRK Hospital Chemnitz-Rabenstein, Rabenstein, Germany.
Beatrice Schell: Department of Dermatology, Wald-Klinikum Gera, Gera 07546, Germany.
Anja Gesierich: Department of Dermatology, University Hospital W��rzburg, W��rzburg, Germany.
Carmen Loquai: Department of Dermatology, Klinikum Bremen-Ost, Gesundheit Nord gGmbH, Bremen, Germany.
Jessica C Hassel: Heidelberg University, Medical Faculty Heidelberg, Department of Dermatology and National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and University Hospital Heidelberg, Heidelberg, Germany.
Jens Ulrich: Department of Dermatology and Allergy, Harzklinikum Dorothea Christiane Erxleben GmbH, Quedlinburg, Germany.
Frank Meiss: Department of Dermatology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Gaston Schley: Department of Dermatology, HELIOS Hospital Schwerin, Schwerin, Germany.
Lucie M Heinzerling: Department of Dermatology and Allergy, University Hospital, Ludwig-Maximilian Universit��t Munich, M��nchen, Germany.
Michael Sachse: Department of Dermatology, Hospital Bremerhaven Reinkenheide, Bremerhaven, Germany.
Julia Welzel: Department of Dermatology, University Hospital Augsburg, Augsburg, Germany.
Carsten Weishaupt: Department of Dermatology, University Hospital of Muenster, Muenster, Germany.
Cord Sunderk��tter: Department of Dermatology and Venereology, Martin Luther University Halle-Wittenberg, Halle, Germany.
Christiane Michl: Department of Dermatology and Venereology, Martin Luther University Halle-Wittenberg, Halle, Germany.
Harm-Henning Lindhof: Department of Dermatology, Universit��tsklinikum D��sseldorf, Dusseldorf, Germany.
Alexander Kreuter: Department of Dermatology, Venerology and Allergology, Helios St. Elisabeth Klinik Oberhausen, University Witten-Herdecke, Oberhausen, Germany.
Markus V Heppt: Department of Dermatology, Uniklinikum Erlangen, Friedrich-Alexander University Erlangen-N��rnberg (FAU), Comprehensive Cancer Center Erlangen-European Metropolitan Area of Nuremberg (CCC ER-EMN) and CCC Alliance WERA, Bavarian Cancer Research Center (BZKF), Erlangen 91052, Germany.
Saskia Wenk: Department of Dermatology, Medical Center Klinikum Darmstadt, Teaching Hospital Goethe-University Frankfurt, Darmstadt, Germany.
Cornelia Mauch: Department of Dermatology, Ruhr-Universit��t Bochum, Bochum, Germany.
Carola Berking: Department of Dermatology, Uniklinikum Erlangen, Friedrich-Alexander University Erlangen-N��rnberg (FAU), Comprehensive Cancer Center Erlangen-European Metropolitan Area of Nuremberg (CCC ER-EMN) and CCC Alliance WERA, Bavarian Cancer Research Center (BZKF), Erlangen 91052, Germany.
Annekathrin Silvia Nedwed: Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center Mainz, Mainz, Germany.
Ralf Gutzmer: Department of Dermatology, Muehlenkreiskliniken Minden and Ruhr University Bochum, Minden, Germany.
Ulrike Leiter: Center for Dermatooncology, Department of Dermatology, Eberhard-Karls University of T��bingen, Tubingen, Germany.
Dirk Schadendorf: Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany.
Selma Ugurel: Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany.
Michael Weichenthal: Department of Dermatology, Skin Cancer Center, University Hospital Schleswig-Holstein - Campus Kiel, Kiel, Germany.
Maximilian Haist: Department of Dermatology, University Medical Center Mainz, Mainz 55131, Germany.
Maria Isabel Fleischer: Department of Dermatology, University Medical Center Mainz, Mainz 55131, Germany.
Berenice Lang: Department of Dermatology, University Medical Center Mainz, Mainz 55131, Germany.
Stephan Grabbe: Department of Dermatology, University Medical Center Mainz, Mainz 55131, Germany.
Henner Stege: Department of Dermatology, University Medical Center Mainz, Mainz 55131, Germany. Electronic address: Henner.Stege@unimedizin-mainz.de.
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: ALMpatients had significantly higher rates of ulcerated tumors, loco regional metastases and fewer BRAF-mutated tumors compared to CMpatients. Combined CPI was administered in 48.9���% ALMpatients and 39.3���% of CMpatients, 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.
