Early versus late response to PD-1-based immunotherapy in metastatic melanoma

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Georg C. Lodde - , University of Duisburg-Essen (Author)
  • Fang Zhao - , University of Duisburg-Essen (Author)
  • Rudolf Herbst - , Fresenius AG (Author)
  • Patrick Terheyden - , Universitätsklinikum Schleswig-Holstein - Campus Lübeck (Author)
  • Jochen Utikal - , Heidelberg University  (Author)
  • Claudia Pföhler - , Saarland University (Author)
  • Jens Ulrich - , Otto von Guericke University Magdeburg (Author)
  • Alexander Kreuter - , Witten/Herdecke University (Author)
  • Peter Mohr - , Elbe Clinics Stade/Buxtehude (Author)
  • Ralf Gutzmer - , Ruhr University Bochum (Author)
  • Friedegund Meier - , Department of Dermatology, Skin Tumor Center, University Hospital Carl Gustav Carus Dresden (Author)
  • Edgar Dippel - , Klinikum Ludwigshafen (Author)
  • Michael Weichenthal - , University Hospital Schleswig-Holstein Campus Kiel (Author)
  • Philipp Jansen - , University of Bonn (Author)
  • Bernd Kowall - , University of Duisburg-Essen (Author)
  • Wolfgang Galetzka - , University of Duisburg-Essen (Author)
  • Fabian Hörst - , University of Duisburg-Essen (Author)
  • Jens Kleesiek - , University of Duisburg-Essen (Author)
  • Birte Hellwig - , Dortmund University of Technology (Author)
  • Jörg Rahnenführer - , Dortmund University of Technology (Author)
  • Luisa Rajcsanyi - , University of Duisburg-Essen (Author)
  • Triinu Peters - , University of Duisburg-Essen (Author)
  • Anke Hinney - , University of Duisburg-Essen (Author)
  • Jan Malte Placke - , University of Duisburg-Essen, German Cancer Consortium (DKTK) partner site Essen / Düsseldorf (Author)
  • Antje Sucker - , University of Duisburg-Essen (Author)
  • Annette Paschen - , University of Duisburg-Essen, German Cancer Consortium (DKTK) partner site Essen / Düsseldorf (Author)
  • Jürgen C. Becker - , University of Duisburg-Essen, German Cancer Consortium (DKTK) partner site Essen / Düsseldorf (Author)
  • Elisabeth Livingstone - , University of Duisburg-Essen (Author)
  • Lisa Zimmer - , University of Duisburg-Essen, German Cancer Consortium (DKTK) partner site Essen / Düsseldorf (Author)
  • Alpaslan Tasdogan - , University of Duisburg-Essen, German Cancer Consortium (DKTK) partner site Essen / Düsseldorf (Author)
  • Alexander Roesch - , University of Duisburg-Essen, German Cancer Consortium (DKTK) partner site Essen / Düsseldorf (Author)
  • Eva Hadaschik - , University of Duisburg-Essen (Author)
  • Dirk Schadendorf - , University of Duisburg-Essen, German Cancer Consortium (DKTK) partner site Essen / Düsseldorf (Author)
  • Klaus Griewank - , University of Duisburg-Essen (Author)
  • Selma Ugurel - , University of Duisburg-Essen, German Cancer Consortium (DKTK) partner site Essen / Düsseldorf (Author)

Abstract

Background: Immune checkpoint inhibition (ICI) currently is the most effective treatment to induce durable responses in metastatic melanoma. The aims of this study are the characterization of patients with early, late and non-response to ICI and analysis of survival outcomes in a real-world patient cohort. Methods: Patients who received PD-1-based immunotherapy for non-resectable stage-IV melanoma in any therapy line were selected from the prospective multicenter real-world DeCOG study ADOREG-TRIM (NCT05750511). Patients showing complete (CR) or partial (PR) response already during the first 3 months of treatment (Early Responders, EarlyR) were compared to patients showing CR/PR at a later time (Late Responders, LateR), a stable disease (SD) and to patients showing progressive disease (Non-Responders, NonR). Results: Of 522 patients, 8.2 % were EarlyR (n = 43), 19.0 % were LateR (n = 99), 37.0 % had a SD (n = 193) and 35.8 % were NonR (n = 187). EarlyR, LateR and SD patients had comparable baseline characteristics. Multivariate logbinomial regression analyses adjusted for age and sex revealed positive tumor PD-L1 (RR=1.99, 95 %-CI=1.14–3.46, p = 0.015), and normal serum CRP (RR=1.59, 95 %-CI=0.93–2.70, p = 0.036) as independently associated with the achievement of an early response compared to NonR. The median progression-free and overall survival was 46.0 months (95 % CI 19.1; NR) and 47.8 months (95 %-CI 36.9; NR) for EarlyR, NR (95 %-CI NR; NR) for LateR, 8.1 months (7.0; 10.4) and 35.4 months (29.2; NR) for SD, and 2.0 months (95 %-CI 1.9; 2.1) and 6.1 months (95 %-CI 4.6; 8.8) for NonR patients. Conclusion: Less than 10 % of metastatic melanoma patients achieved an early response during the first 3 months of PD-1-based immunotherapy. Early responders were not superior to late responders in terms of response durability and survival.

Details

Original languageEnglish
Article number114295
JournalEuropean journal of cancer
Volume210
Publication statusPublished - Oct 2024
Peer-reviewedYes

External IDs

PubMed 39213786
ORCID /0000-0003-4340-9706/work/169643426

Keywords

ASJC Scopus subject areas

Keywords

  • Best overall response, CTLA-4, Immune checkpoint inhibition, Immunotherapy, Melanoma, PD-1, PD-L1, Survival, Therapy outcome