Digital Quantification of Tumor PD-L1 Predicts Outcome of PD-1-Based Immune Checkpoint Therapy in Metastatic Melanoma
BackgroundPD-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...
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.741993/full |
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| author | Jan-Malte Placke Camille Soun Jenny Bottek Rudolf Herbst Patrick Terheyden Jochen Utikal Jochen Utikal Claudia Pföhler Jens Ulrich Alexander Kreuter Christiane Pfeiffer Peter Mohr Ralf Gutzmer Friedegund Meier Friedegund Meier Edgar Dippel Michael Weichenthal Lisa Zimmer Elisabeth Livingstone Jürgen C. Becker Jürgen C. Becker Jürgen C. Becker Georg Lodde Antje Sucker Klaus Griewank Susanne Horn Eva Hadaschik Alexander Roesch Alexander Roesch Dirk Schadendorf Dirk Schadendorf Daniel Robert Engel Selma Ugurel |
| author_facet | Jan-Malte Placke Camille Soun Jenny Bottek Rudolf Herbst Patrick Terheyden Jochen Utikal Jochen Utikal Claudia Pföhler Jens Ulrich Alexander Kreuter Christiane Pfeiffer Peter Mohr Ralf Gutzmer Friedegund Meier Friedegund Meier Edgar Dippel Michael Weichenthal Lisa Zimmer Elisabeth Livingstone Jürgen C. Becker Jürgen C. Becker Jürgen C. Becker Georg Lodde Antje Sucker Klaus Griewank Susanne Horn Eva Hadaschik Alexander Roesch Alexander Roesch Dirk Schadendorf Dirk Schadendorf Daniel Robert Engel Selma Ugurel |
| author_sort | Jan-Malte Placke |
| collection | DOAJ |
| description | BackgroundPD-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 MethodsTumor 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).ResultsTissue 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).ConclusionPre-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. |
| first_indexed | 2024-12-17T05:23:59Z |
| format | Article |
| id | doaj.art-967680da967d4d1da0a6265a5de347ab |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-17T05:23:59Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-967680da967d4d1da0a6265a5de347ab2022-12-21T22:01:56ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-09-011110.3389/fonc.2021.741993741993Digital Quantification of Tumor PD-L1 Predicts Outcome of PD-1-Based Immune Checkpoint Therapy in Metastatic MelanomaJan-Malte Placke0Camille Soun1Jenny Bottek2Rudolf Herbst3Patrick Terheyden4Jochen Utikal5Jochen Utikal6Claudia Pföhler7Jens Ulrich8Alexander Kreuter9Christiane Pfeiffer10Peter Mohr11Ralf Gutzmer12Friedegund Meier13Friedegund Meier14Edgar Dippel15Michael Weichenthal16Lisa Zimmer17Elisabeth Livingstone18Jürgen C. Becker19Jürgen C. Becker20Jürgen C. Becker21Georg Lodde22Antje Sucker23Klaus Griewank24Susanne Horn25Eva Hadaschik26Alexander Roesch27Alexander Roesch28Dirk Schadendorf29Dirk Schadendorf30Daniel Robert Engel31Selma Ugurel32Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyInstitute of Experimental Immunology and Imaging, Department of Immunodynamics, University Hospital Essen, Essen, GermanyInstitute of Experimental Immunology and Imaging, Department of Immunodynamics, University Hospital Essen, Essen, GermanyDepartment of Dermatology, Medical Hospital, Erfurt, GermanyDepartment of Dermatology, University of Lübeck, Lübeck, GermanyDepartment of Dermatology, Venerology, and Allergology, University Medical Center, Ruprecht-Karls University of Heidelberg, Mannheim, GermanyGerman Consortium of Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, GermanyDepartment of Dermatology, Saarland University Medical School, Homburg, GermanyDepartment of Dermatology, Medical Hospital of Quedlinburg, Quedlinburg, GermanyDepartment of Dermatology, Venereology, and Allergology, Helios St. Elisabeth Hospital Oberhausen, University of Witten-Herdecke, Oberhausen, Germany0Department of Dermatology, Venereology, and Allergology University Ulm, Ulm, Germany1Department of Dermatology, Elbe-Kliniken, Buxtehude, Germany2Skin Cancer Center, Department of Dermatology, Hannover Medical School, Hannover, GermanyGerman Consortium of Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany3Department of Dermatology, University Hospital Dresden, Dresden, Germany4Hautklinik, Klinikum der Stadt Ludwigshafen am Rhein gGmbH, Ludwigshafen, Germany5Department of Dermatology, University Hospital Kiel, Kiel, GermanyDepartment of Dermatology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyDepartment of Dermatology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyDepartment of Dermatology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyGerman Consortium of Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany6Translationale Hautkrebsforschung, University Medicine Essen, University of Duisburg-Essen, Essen, GermanyDepartment of Dermatology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyDepartment of Dermatology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyDepartment of Dermatology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyDepartment of Dermatology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyDepartment of Dermatology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyDepartment of Dermatology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyGerman Consortium of Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, GermanyDepartment of Dermatology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyGerman Consortium of Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, GermanyInstitute of Experimental Immunology and Imaging, Department of Immunodynamics, University Hospital Essen, Essen, GermanyDepartment of Dermatology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyBackgroundPD-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 MethodsTumor 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).ResultsTissue 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).ConclusionPre-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.https://www.frontiersin.org/articles/10.3389/fonc.2021.741993/fullPD-L1 quantificationmelanomaimmune checkpoint blockade therapyresponsesurvival |
| spellingShingle | Jan-Malte Placke Camille Soun Jenny Bottek Rudolf Herbst Patrick Terheyden Jochen Utikal Jochen Utikal Claudia Pföhler Jens Ulrich Alexander Kreuter Christiane Pfeiffer Peter Mohr Ralf Gutzmer Friedegund Meier Friedegund Meier Edgar Dippel Michael Weichenthal Lisa Zimmer Elisabeth Livingstone Jürgen C. Becker Jürgen C. Becker Jürgen C. Becker Georg Lodde Antje Sucker Klaus Griewank Susanne Horn Eva Hadaschik Alexander Roesch Alexander Roesch Dirk Schadendorf Dirk Schadendorf Daniel Robert Engel Selma Ugurel Digital Quantification of Tumor PD-L1 Predicts Outcome of PD-1-Based Immune Checkpoint Therapy in Metastatic Melanoma Frontiers in Oncology PD-L1 quantification melanoma immune checkpoint blockade therapy response survival |
| title | Digital Quantification of Tumor PD-L1 Predicts Outcome of PD-1-Based Immune Checkpoint Therapy in Metastatic Melanoma |
| title_full | Digital Quantification of Tumor PD-L1 Predicts Outcome of PD-1-Based Immune Checkpoint Therapy in Metastatic Melanoma |
| title_fullStr | Digital Quantification of Tumor PD-L1 Predicts Outcome of PD-1-Based Immune Checkpoint Therapy in Metastatic Melanoma |
| title_full_unstemmed | Digital Quantification of Tumor PD-L1 Predicts Outcome of PD-1-Based Immune Checkpoint Therapy in Metastatic Melanoma |
| title_short | Digital Quantification of Tumor PD-L1 Predicts Outcome of PD-1-Based Immune Checkpoint Therapy in Metastatic Melanoma |
| title_sort | digital quantification of tumor pd l1 predicts outcome of pd 1 based immune checkpoint therapy in metastatic melanoma |
| topic | PD-L1 quantification melanoma immune checkpoint blockade therapy response survival |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.741993/full |
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