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

Georg C Lodde, Fang Zhao, Rudolf Herbst, Patrick Terheyden, Jochen Utikal, Claudia Pföhler, Jens Ulrich, Alexander Kreuter, Peter Mohr, Ralf Gutzmer, Friedegund Meier, Edgar Dippel, Michael Weichenthal, Philipp Jansen, Bernd Kowall, Wolfgang Galetzka, Fabian Hörst, Jens Kleesiek, Birte Hellwig, Jörg Rahnenführer, Luisa Rajcsanyi, Triinu Peters, Anke Hinney, Jan-Malte Placke, Antje Sucker, Annette Paschen, Jürgen C. Becker, Elisabeth Livingstone, Lisa Zimmer, Alpaslan Tasdogan, Alexander Roesch, Eva Hadaschik, Dirk Schadendorf, Klaus Griewank, Selma Ugurel
August 2024
Cite Doi ScienceDirect

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.

Type
Journal article
Melanoma Immune checkpoint inhibition Immunotherapy PD-L1 PD-1 CTLA-4 therapy outcome best overall response survival
Wolfgang Galetzka
Wolfgang Galetzka
Researcher in the first cohort

My research interests include Deep Learning, Computer Vision, Radiomics, and Explainable AI.

Jens Kleesiek
Jens Kleesiek
Principal Investigator
Elisabeth Livingstone
Elisabeth Livingstone
Principal Investigator

My research interests include Medical Research, Dermatology, and Digitalization.

Dirk Schadendorf
Dirk Schadendorf
Principal Investigator

My research interests include Dermatology, Medical Research, and Digitalization.

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