دورية أكاديمية
Digital quantification of tumor PD-L1 predicts outcome of PD-1-based immune checkpoint therapy in metastatic melanoma
| العنوان: | Digital quantification of tumor PD-L1 predicts outcome of PD-1-based immune checkpoint therapy in metastatic melanoma |
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| المؤلفون: | 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, Schadendorf, Dirk, Engel, Daniel Robert, Ugurel, Selma |
| بيانات النشر: | Universität Ulm |
| سنة النشر: | 2023 |
| المجموعة: | OPARU (OPen Access Repository of Ulm University) |
| مصطلحات موضوعية: | PD-L1 quantification, immune checkpoint blockade therapy, response, DDC 610 / Medicine & health, Melanoma, Immunology, Immunotherapy, Methods, Survival, Melanom, Metastase, Immuntherapie, Überleben |
| الوصف: | Background 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. Patients and Methods 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). Results 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% versus 32.2%; p=0.026) and physician (BOR 54.2% versus 36.6%; p=0.032) quantification. Tumor PD-L1 positivity was associated with a prolonged PFS and OS by either digital (PFS, 9.9 versus 4.6 months, p=0.021; OS, not reached versus 13.0 months, p=0.001) or physician (PFS, 10.6 versus 5.6 months, p=0.051; OS, not reached versus 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). Conclusion 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. ; publishedVersion |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf; image/tiff; application/octet-stream |
| اللغة: | English |
| العلاقة: | https://www.frontiersin.org/articles/10.3389/fonc.2021.741993/full#supplementary-materialTest; http://dx.doi.org/10.18725/OPARU-48460Test; https://oparu.uni-ulm.de/xmlui/123456789/48536Test; http://nbn-resolving.de/urn:nbn:de:bsz:289-oparu-48536-4Test |
| DOI: | 10.18725/OPARU-48460 |
| الإتاحة: | https://doi.org/10.18725/OPARU-48460Test https://oparu.uni-ulm.de/xmlui/123456789/48536Test http://nbn-resolving.de/urn:nbn:de:bsz:289-oparu-48536-4Test |
| حقوق: | CC BY 4.0 International ; https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.C066EFFE |
| قاعدة البيانات: | BASE |
| DOI: | 10.18725/OPARU-48460 |
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