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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1536642
This article is part of the Research Topic Immunology and Immunotherapy of Skin Cancer View all 14 articles

Presence of brain metastasis differentially impacts long-term survival after first-line therapy in melanoma depending on BRAF mutation status

Provisionally accepted
Jan-Malte Placke Jan-Malte Placke 1*Luisa Sophie Rajcsanyi Luisa Sophie Rajcsanyi 1Rudolf Herbst Rudolf Herbst 2Patrick Terheyden Patrick Terheyden 3Jochen Utikal Jochen Utikal 4Claudia Pföhler Claudia Pföhler 5Alexander Kreuter Alexander Kreuter 6Peter Mohr Peter Mohr 7Ralf Gutzmer Ralf Gutzmer 8Michael Weichenthal Michael Weichenthal 3Friedegund Meier Friedegund Meier 9Carola Berking Carola Berking 10Ulrike Leiter Ulrike Leiter 11Johanna Seier Johanna Seier 1Frederik Krefting Frederik Krefting 1Alpaslan Tasdogan Alpaslan Tasdogan 1Georg Christian Lodde Georg Christian Lodde 1Elisabeth Livingstone Elisabeth Livingstone 1Lisa Zimmer Lisa Zimmer 1Alexander Roesch Alexander Roesch 1Klaus Griewank Klaus Griewank 1Dirk Schadendorf Dirk Schadendorf 1Selma Ugurel Selma Ugurel 1
  • 1 University of Duisburg-Essen, Duisburg, Germany
  • 2 Helios Hospital Erfurt, Erfurt, Thuringia, Germany
  • 3 Department of Dermatology, Allergology and Venereology, University Hospital Schleswig-Holstein, Lübeck, Schleswig-Holstein, Germany
  • 4 Skin Cancer Unit, German Cancer Research Center, Heidelberg, Baden-Württemberg, Germany
  • 5 Department of Dermatology, Saarland University Medical School, Homburg/Saar, Germany
  • 6 HELIOS St. Elisabeth Klinik Oberhausen, Oberhausen, Germany
  • 7 Elbe Kliniken, Buxtehude, Germany
  • 8 Skin Cancer Center Minden, Minden, Germany
  • 9 University Hospital Carl Gustav Carus, Dresden, Lower Saxony, Germany
  • 10 Department of Dermatology, University Hospital Erlangen, Erlangen, Bavaria, Germany
  • 11 Department of Dermatology, University Hospital Tübingen, Tübingen, Baden-Württemberg, Germany

The final, formatted version of the article will be published soon.

    Modern therapeutic strategies have significantly improved the prognosis of advanced melanoma patients. Predictive factors of therapy response include serum LDH; however, predictive markers for long-term survival are currently largely lacking.Patients diagnosed with stage IV melanoma (AJCCv8) of cutaneous origin or unknown primary were identified from the prospective multicenter German Dermatologic Cooperative Oncology Group (DeCOG) skin cancer registry ADOREG. Baseline characteristics were compared between patient groups with short-term versus long-term survival. Statistical analysis included ROC analysis and multinomial regression analysis.Of 3066 stage IV melanoma patients entered into the ADOREG between 05/2014 and 06/2021, 395 were identified for this study, of whom 301 (76.2%) survived ≤1 year, and 94 (23.8%) survived ≥5 years after stage IV diagnosis. The median follow-up time was 6 months (range 0-129 months). Regarding the baseline characteristics, only elevated serum LDH (P <0.001) was found to be independently predicting survival ≤1 year. Type of first-line therapy, immune checkpoint inhibition (ICI) versus BRAF/MEK targeted therapy (TT), was not predictive of long-term survival ≥5 years. For survival ≤1 year, the presence of brain metastases at treatment start was an independent predictor year in BRAF-mutated patients regardless if they received TT (N=113; P=0<0.001) or ICI (N=69; P=0.015), but not in BRAF-wildtype patients who received ICI (N=161; P=0.47).Low serum LDH independently predicts long-term survival of stage IV melanoma patients in every subgroup of treatment type and BRAF status. Brain metastasis has a negative impact on long-term

    Keywords: brain metastases, BRAF, Immune check inhibitor (ICI), targeted therapy, Melanoma, Long-term survival

    Received: 29 Nov 2024; Accepted: 29 Jan 2025.

    Copyright: © 2025 Placke, Rajcsanyi, Herbst, Terheyden, Utikal, Pföhler, Kreuter, Mohr, Gutzmer, Weichenthal, Meier, Berking, Leiter, Seier, Krefting, Tasdogan, Lodde, Livingstone, Zimmer, Roesch, Griewank, Schadendorf and Ugurel. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Jan-Malte Placke, University of Duisburg-Essen, Duisburg, Germany

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