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Placke, Jan-Malte; Soun, Camille; Bottek, Jenny; Herbst, Rudolf; Terheyden, Patrick; Utikal, Jochen; Pföhler, Claudia; Ulrich, Jens; Kreuter, Alexander; Pfeiffer, Christiane; Mohr, Peter; Gutzmer, Ralf; Meier, Friedegund; Dippel, Edgar; Weichenthal, Michael; Zimmer, Lisa; Livingstone, Elisabeth; Becker, Jürgen C.; Lodde, Georg; Sucker, Antje; Griewank, Klaus; Horn, Susanne; Hadaschik, Eva; Roesch, Alexander; [...]

Digital Quantification of Tumor PD-L1 Predicts Outcome of PD-1-Based Immune Checkpoint Therapy in Metastatic Melanoma

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  • Medientyp: E-Artikel
  • Titel: Digital Quantification of Tumor PD-L1 Predicts Outcome of PD-1-Based Immune Checkpoint Therapy in Metastatic Melanoma
  • Beteiligte: Placke, Jan-Malte; Soun, Camille; Bottek, Jenny; Herbst, Rudolf; Terheyden, Patrick; Utikal, Jochen; Pföhler, Claudia; Ulrich, Jens; Kreuter, Alexander; Pfeiffer, Christiane; Mohr, Peter; Gutzmer, Ralf; Meier, Friedegund; Dippel, Edgar; Weichenthal, Michael; Zimmer, Lisa; Livingstone, Elisabeth; Becker, Jürgen C.; Lodde, Georg; Sucker, Antje; Griewank, Klaus; Horn, Susanne; Hadaschik, Eva; Roesch, Alexander; [...]
  • Erschienen: Frontiers Media SA, 2021
  • Erschienen in: Frontiers in Oncology
  • Sprache: Nicht zu entscheiden
  • DOI: 10.3389/fonc.2021.741993
  • ISSN: 2234-943X
  • Schlagwörter: Cancer Research ; Oncology
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:sec><jats:title>Background</jats:title><jats:p>PD-1-based immune checkpoint blockade (ICB) is a highly effective therapy in metastatic melanoma. However, 40-60% of patients are primarily resistant, with valid predictive biomarkers currently missing. This study investigated the digitally quantified tumor PD-L1 expression for ICB therapy outcome prediction.</jats:p></jats:sec><jats:sec><jats:title>Patients and Methods</jats:title><jats:p>Tumor tissues taken prior to PD-1-based ICB for unresectable metastatic disease were collected within the prospective multicenter Tissue Registry in Melanoma (TRIM). PD-L1 expression (clone 28-8; cut-off=5%) was determined by digital and physician quantification, and correlated with therapy outcome (best overall response, BOR; progression-free survival, PFS; overall survival, OS).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Tissue samples from 156 patients were analyzed (anti-PD-1, n=115; anti-CTLA-4+anti-PD-1, n=41). Patients with PD-L1-positive tumors showed an improved response compared to patients with PD-L1-negative tumors, by digital (BOR 50.5% <jats:italic>versus</jats:italic> 32.2%; p=0.026) and physician (BOR 54.2% <jats:italic>versus</jats:italic> 36.6%; p=0.032) quantification. Tumor PD-L1 positivity was associated with a prolonged PFS and OS by either digital (PFS, 9.9 <jats:italic>versus</jats:italic> 4.6 months, p=0.021; OS, not reached <jats:italic>versus</jats:italic> 13.0 months, p=0.001) or physician (PFS, 10.6 <jats:italic>versus</jats:italic> 5.6 months, p=0.051; OS, not reached <jats:italic>versus</jats:italic> 15.6 months, p=0.011) quantification. Multivariable Cox regression revealed digital (PFS, HR=0.57, p=0.007; OS, HR=0.44, p=0.001) and physician (OS, HR=0.54, p=0.016) PD-L1 quantification as independent predictors of survival upon PD-1-based ICB. The combination of both methods identified a patient subgroup with particularly favorable therapy outcome (PFS, HR=0.53, p=0.011; OS, HR=0.47, p=0.008).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Pre-treatment tumor PD-L1 positivity predicted a favorable outcome of PD-1-based ICB in melanoma. Herein, digital quantification was not inferior to physician quantification, and should be further validated for clinical use.</jats:p></jats:sec>
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