1168P - Tumor PD-L1 predicts the outcome of PD-1-based immunotherapy in metastatic melanoma depending on the type of tissue examined

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. Here, we systematically investigated whether the type of tumor tissue examined for PD-L1 expression has an impact on ICI therapy outcome prediction.

Methods

Pre-treatment tumor tissue obtained before 1^st ICI therapy for non-resectable stage III/IV metastatic melanoma was prospectively collected within the DeCOG multicenter study Tissue Registry in Melanoma. Stratified by tissue type, best overall response (BOR), progression-free survival (PFS), and overall survival (OS) were correlated with tumor PD-L1 expression (cutoff ≥5%).

Results

Of 448 patients, tumor PD-L1 was determined on 95 primary tumors (PT; 36.8% positivity), 153 skin (34.0% positivity), 115 lymph node (LN; 50.4% positivity), and 85 organ (40.8% positivity) metastases. Skin metastases were significantly more often classified as PD-L1 negative than LN metastases (OR=0.751; 95%CI=0.599-0.956; P=0.007). PD-L1 positivity was predictive for BOR if determined on LN (CR/PR 37.5% versus 16.1%; OR=0.319; 95%CI=0.138-0.76; P=0.010), but not on skin metastases (CR/PR 36.0% versus 28.0%; OR=0.778; 95%CI=0.379-1.554; P=0.49), translating into favorable survival for PD-L1 positivity determined on LN metastases (median PFS 22.0 versus 3.5 months, HR=0.490; 95%CI=0.310-0.775; P=0.002; median OS 68.9 versus 16.6 months, HR=0.519; 95%CI=0.307-0.880P=0.014). PD-L1 positivity determined on 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 predictive to a lesser extent. No relevant survival differences were detected by PD-L1 determined on skin metastases. Multivariate analysis revealed tumor PD-L1 determined on LN metastases as independent predictive factor for PFS (HR=0.43; 95%CI=0.24-0.75; P=0.003) and OS (HR=0.51; 95%CI=0.27-0.96; P=0.037).

Conclusions

For outcome prediction of PD-1-based immunotherapy in melanoma, tumor PD-L1 determined on LN metastases was more reliable than that assessed on PT. PD-L1 determined on skin metastases showed no predictive value and cannot be recommended for clinical use.

Clinical trial identification

CA209-578.

Editorial acknowledgement

Legal entity responsible for the study

Dirk Schadendorf.

Funding

BMS.

Disclosure

J. Placke: Financial Interests, Personal, Funding: BMS; Financial Interests, Personal, Advisory Board: Novartis, Sanofi, Pierre Fabre, Therakos. P. Terheyden: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Novartis, Merck Sharp & Dohme, Pierre Fabre, CureVac, Sanofi, Roche, Kyowa Kirin, Biofrontera. J. Utikal: Financial Interests, Personal, Advisory Board: Amgen, Bristol Myers Squibb, Immunocore, Merck Sharp & Dohme, Novartis, Pierre Fabre, Roche, Sanofi. C. Pfoehler: Financial Interests, Personal, Advisory Board: Novartis, Bristol Myers Squibb, MSD, Merck, Celgene, AbbVie, Sun Pharma, Pierre Fabre, UCB, Nutricia Milupa, Janssen, Leo. P. Mohr: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Beiersdorf, Merck Sharp & Dohme, Pierre Fabre, Sun Pharma, Immunocore, Novartis. R. Gutzmer: Financial Interests, Personal, Advisory Board: Roche, BMS, MSD, Novartis, Amgen, Merck, Sun Pharma, Sanofi, Pierre Fabre, 4SC, Immunocore. F. Meier: Financial Interests, Personal, Advisory Board: Novartis, Roche, BMS, MSD, Pierre Fabre, Sanofi, Immunocore. J.C. Becker: Financial Interests, Personal, Advisory Board: Amgen, Merck, Recordati, Sanofi, Boehringer Ingelheim, InProTher, Almirall; Financial Interests, Personal, Other, Member of a DMSB: 4SC; Financial Interests, Institutional, Research Grant: IQVIA, Alcedis, Merck; Non-Financial Interests, Institutional, Product Samples: 4SC. D. Schadendorf: Financial Interests, Personal, Invited Speaker: BMS, Novartis, MSD, Roche, Merck Serono, Sanofi; Financial Interests, Personal, Advisory Board: BMS, Novartis, MSD, Immunocore, Pierre Fabre, Sanofi/Regeneron, Pfizer, Philogen, Neracare; Financial Interests, Personal, Steering Committee Member: Novartis, BMS, MSD; Financial Interests, Institutional, Coordinating PI: Novartis, BMS, MSD, Pierre Fabre; Financial Interests, Institutional, Research Grant: BMS, MSD; Financial Interests, Institutional, Local PI: Sanofi, Philogen; Non-Financial Interests, Member of Board of Directors: EORTC-MG. S. Ugurel-Becker: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Merck Serono, Merck Sharp & Dohme, Novartis. All other authors have declared no conflicts of interest.