Baseline-derived neutrophil-to-lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) to predict the benefit of immune checkpoint inhibitors (ICI) in advanced non-small cell lung cancer (NSCLC) patients.

Abstract

9089 Background: dNRL (Neutrophils/Leucocytes-Neutrophils) and LDH were recently correlated to ICI benefit in melanoma. We tested if dNLR and LDH could have the same role in NSCLC patients. Methods: Baseline dNLR and LDH were collected in 234 patients treated with PD1/PDL1 inhibitors from Nov. 2013 to Dec. 2016, in a discovery (D) cohort (N = 161) from Gustave Roussy and an independent validation (V) cohort (N = 73) from 2 centers. ICI benefit was analyzed according to overall survival (OS), progression free survival (PFS) and response rate (RR) by RECIST 1.1. Kaplan-Meier and Cox regression were performed. Results: In the D cohort, 100 patients (62%) were males, 136 (85%) smokers and PS ≤1, with median age 61.5; 133 patients (81%) stage IV; 100 (62%) had adenocarcinoma and 46 (29%) squamous cells carcinoma; 35 (22%) were KRASmut, 13 (8%) EGFRmut and 3 (2%) ALKpositive. PDL1 expression was positive in 43 (75%), negative in 14 (25%) and unknown in 78. 132 (82%) patients received PD1 inhibitors; the median of prior lines was 1 (1-11). dNLR > 3 and LDH > upper normal limit (UNL) were independent factors for poor OS (HR 4,67, p = 0.011 and HR 2,65, p = 0.002, respectively) and poor PFS (HR 4,71, p = 0.001 and HR 1,68, p = 0.042 respectively). The median follow-up (FU) was 12 months (m) [95% CI 11-14], the median PFS 3m [2-4] and the median OS 10m [8-13]. In the V cohort, with a median FU of 11m [8-14], dNLR > 3 and LDH > UNL were significantly associated with poor OS (both p = 0.001), with a trend toward association with PFS (p = 0.06, p = 0.08, respectively). A Lung Immune Predictive Index (LIPI) was tested considering dNLR > 3 and LDH > UNL, with three groups. In D cohort, the median OS for good (no factor), intermediate (one factor) and poor (two factors) was 34m [17-NR], 10m [8-NR], 3m [1-NR], respectively (p = 0.0001), and PFS was similarly correlated (p = 0.001). Same results were demonstrated in the V cohort. Conclusions: Baseline dNLR > 3 and LDH > UNL can predict the benefit of ICI in advanced NSCLC patients. The LIPI at baseline is an easy tool to identify the candidates to immunotherapy. Confirmation cohorts are ongoing to validate the predictive role of the LIPI.