Correlation of tumor PD-L1 expression in different tissue types and outcome of PD-1-based immunotherapy in metastatic melanoma – analysis of the DeCOG prospective multicenter cohort study ADOREG/TRIM

Jan Malte Placke, Mona Kimmig, Klaus Griewank, Rudolf Herbst, Patrick Terheyden, Jochen Utikal, Claudia Pföhler, Jens Ulrich, Alexander Kreuter, Peter Mohr, Ralf Gutzmer, Friedegund Meier, Edgar Dippel, Julia Welzel, Daniel Robert Engel, Sophia Kreft, Antje Sucker, Georg Lodde, Frederik Krefting, Ingo StoffelsJoachim Klode, Alexander Roesch, Lisa Zimmer, Elisabeth Livingstone, Eva Hadaschik, Jürgen C. Becker, Michael Weichenthal, Alpaslan Tasdogan, Dirk Schadendorf, Selma Ugurel*

*Corresponding author for this work
4 Citations (Scopus)

Abstract

Background: PD-1-based immune checkpoint inhibition (ICI) is the major backbone of current melanoma therapy. Tumor PD-L1 expression represents one of few biomarkers predicting ICI therapy outcome. The objective of the present study was to systematically investigate whether the type of tumor tissue examined for PD-L1 expression has an impact on the correlation with ICI therapy outcome. Methods: Pre-treatment tumor tissue was collected within the prospective DeCOG cohort study ADOREG/TRIM (CA209-578; NCT05750511) between February 2014 and May 2020 from 448 consecutive patients who received PD-1-based ICI for non-resectable metastatic melanoma. The primary study endpoint was best overall response (BOR), secondary endpoints were progression-free (PFS) and overall survival (OS). All endpoints were correlated with tumor PD-L1 expression (quantified with clone 28–8; cutoff ≥5%) and stratified by tissue type. Findings: Tumor PD-L1 was determined in 95 primary tumors (PT; 36.8% positivity), 153 skin/subcutaneous (34.0% positivity), 115 lymph node (LN; 50.4% positivity), and 85 organ (40.8% positivity) metastases. Tumor PD-L1 correlated with BOR if determined in LN (OR = 0.319; 95% CI = 0.138–0.762; P = 0.010), but not in skin/subcutaneous metastases (OR = 0.656; 95% CI = 0.311–1.341; P = 0.26). PD-L1 positivity determined on LN metastases was associated with favorable survival (PFS, HR = 0.490; 95% CI = 0.310–0.775; P = 0.002; OS, HR = 0.519; 95% CI = 0.307–0.880; P = 0.014). PD-L1 positivity determined in PT (PFS, HR = 0.757; 95% CI = 0.467–1.226; P = 0.27; OS; HR = 0.528; 95% CI = 0.305–0.913; P = 0.032) was correlated with survival to a lesser extent. No relevant survival differences were detected by PD-L1 determined in skin/subcutaneous metastases (PFS, HR = 0.825; 95% CI = 0.555–1.226; P = 0.35; OS, HR = 1.083; 95% CI = 0.698–1.681; P = 0.72). Interpretation: For PD-1-based immunotherapy in melanoma, tumor PD-L1 determined in LN metastases was stronger correlated with therapy outcome than that assessed in PT or organ metastases. PD-L1 determined in skin/subcutaneous metastases showed no outcome correlation and therefore should be used with caution for clinical decision making. Funding: Bristol-Myers Squibb (ADOREG/TRIM, NCT05750511); German Research Foundation (DFG; Clinician Scientist Program UMEA); Else Kröner-Fresenius-Stiftung (EKFS; Medical Scientist Academy UMESciA).

Original languageEnglish
Article number104774
JournalEBioMedicine
Volume96
DOIs
Publication statusPublished - 10.2023

Research Areas and Centers

  • Research Area: Luebeck Integrated Oncology Network (LION)
  • Centers: University Cancer Center Schleswig-Holstein (UCCSH)

DFG Research Classification Scheme

  • 205-19 Dermatology

Cite this