P57.02 Integration of Systemic / Tumor PD-L1 as a Predictive Biomarker of Clinical Outcome in Advanced NSCLC Patients Treated With Anti-PD-(L)1 Agents

Abstract

Tumor PD-L1 expression is a predictive biomarker for NSCLC patients (pts) receiving anti-PD-(L)1 agents. However, clinical benefit has been observed regardless of tumor PD-L1 expression, suggesting the existence of other PD-L1 sources. The aim of our study was to analyze whether integrating systemic and tumor PD-L1 is more predictive of outcome in advanced NSCLC pts receiving PD-(L)1 blockade agents. Pretreatment blood samples were collected to evaluate PD-L1 levels on circulating immune cells, platelets (PLTs), platelet microparticles (PMPs) and plasmatic concentrations of soluble PD-L1 (sPD-L1). Tumor PD-L1 status was assessed by immunohistochemistry. The percentages of circulating PD-L1+ leukocytes, PLTs, sPD-L1 levels and tumor PD-L1 expression were correlated with clinical outcome. 29 healthy donors and 119 advanced NSCLC pts treated with anti-PD-(L)1 were prospectively included. Median follow-up: 10.97 months [IQR: 6.06-21.87]. Median age of NSCLC patients was 65 (36-84), 78.1% were male and the most common histology was non-squamous (61.3%). Tumor PD-L1 expression (IHC 22C3 pharmDx) : <1% 30 pts (25.2%), 1-49% 35 (29.4%), ≥50% 37 (31.1%), not evaluable 17 (14.3%). PD-(L)1 inhibitors were given in 1st line in 37 pts (31.1%) and in ≥2nd line in 82 (68.9%), and given as monotherapy in 104 pts (87.4%), combination with chemotherapy in 11 pts (9.2%), or with other immunotherapy in 4 pts (3.4%) pts. Significantly longer progression free survival was observed in pts with higher percentage of PD-L1+ CD14+, PD-L1+ neutrophils, PD-L1+ PLTs and PD-L1+ PMPs and significantly longer overall survival was observed in pts with higher percentages of PD-L1+ CD14+ and high tumor PD-L1 expression (Table 1). Higher levels of integrated PD-L1 data of circulating and tumor PD-L1 results significantly stratified patients according to efficacy of PD-(L1) blockade agents (PFS: HR 0.29; 95% CI: 0.16-0.54, p<0.0001; OS: HR 0.28; 95% CI: 0.14-0.54, p=0.0002), even when tumor PD-L1 expression was excluded.Table 1PFSOSVariablesHR95% CIPHR95% CIP% PD-L1+ CD4+0.760.44-1.320.330.790.45-1.390.42% PD-L1+ CD8+0.690.41-1.160.160.810.47 – 1.390.45% PD-L1+ NK1.170.69-1.990.551.10.63 – 1.90.72% PD-L1+ CD14+0.360.22-0.58<0.0010.580.37- 0.930.02% PD-L1+ Neutrophils0.510.32-0.8<0.010.680.43–1.070.09% PD-L1+ PLTs0.480.26-0.880.020.970.51-1.960.93% PD-L1+ PMPs0.490.28-0.870.020.570.29-1.10.09pg/ml sPD-L11.260.81-1.970.291.240.78-1.970.34% TPS ≥50% vs <1% ≥50% vs 1-49%0.65 0.610.36-1.18 0.32 - 1.150.23 0.230.47 0.590.24-0.91 0.31-1.120.02 0.02 Open table in a new tab Our results suggest that the integration of circulating PD-L1+ leukocytes, PLT, PMPs and sPD-L1 and tumor PD-L1 expression could be helpful to decide the best treatment strategy in advanced NSCLC pts candidates for anti-PD-(L)1 agents.