TY - JOUR
T1 - Digital Quantification of Tumor PD-L1 Predicts Outcome of PD-1-Based Immune Checkpoint Therapy in Metastatic Melanoma
AU - Placke, Jan Malte
AU - Soun, Camille
AU - Bottek, Jenny
AU - Herbst, Rudolf
AU - Terheyden, Patrick
AU - Utikal, Jochen
AU - Pföhler, Claudia
AU - Ulrich, Jens
AU - Kreuter, Alexander
AU - Pfeiffer, Christiane
AU - Mohr, Peter
AU - Gutzmer, Ralf
AU - Meier, Friedegund
AU - Dippel, Edgar
AU - Weichenthal, Michael
AU - Zimmer, Lisa
AU - Livingstone, Elisabeth
AU - Becker, Jürgen C.
AU - Lodde, Georg
AU - Sucker, Antje
AU - Griewank, Klaus
AU - Horn, Susanne
AU - Hadaschik, Eva
AU - Roesch, Alexander
AU - Schadendorf, Dirk
AU - Engel, Daniel Robert
AU - Ugurel, Selma
N1 - Publisher Copyright:
© Copyright © 2021 Placke, Soun, Bottek, Herbst, Terheyden, Utikal, Pföhler, Ulrich, Kreuter, Pfeiffer, Mohr, Gutzmer, Meier, Dippel, Weichenthal, Zimmer, Livingstone, Becker, Lodde, Sucker, Griewank, Horn, Hadaschik, Roesch, Schadendorf, Engel and Ugurel.
PY - 2021/9/21
Y1 - 2021/9/21
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85116499494&partnerID=8YFLogxK
U2 - 10.3389/fonc.2021.741993
DO - 10.3389/fonc.2021.741993
M3 - Journal articles
AN - SCOPUS:85116499494
SN - 2234-943X
VL - 11
JO - Frontiers in Oncology
JF - Frontiers in Oncology
M1 - 741993
ER -
