External validation and longitudinal extension of the LIPI (Lung Immune Prognostic Index) for immunotherapy outcomes in advanced non-small cell lung cancer

Background The Lung Immune Prognostic Index (LIPI), consisting of an elevated derived neutrophil-lymphocyte ratio (dNLR, 1 point for dNLR > 3 units) and an elevated lactate dehydrogenase level (LDH, 1 point for LDH > upper limit of normal) has recently been proposed as a biomarker for predicting immune checkpoint inhibitor (ICI) therapy outcomes in advanced non-small cell lung cancer (NSCLC). We sought to validate the LIPI in an external cohort, and quantify the evolution of the LIPI over time during ICI therapy. Methods dNLR levels, LDH levels and ICI treatment outcomes including disease control rate (DCR), 1-year progression-free survival (PFS), and 1-year overall survival (OS) were ascertained from 87 patients with advanced NSCLC who were treated with ICIs at a single academic center in Austria (Table). Results DCR estimates were 59%, 43%, and 32% in patients with good (0 points, n = 22), intermediate (1 point, n = 40), and poor (2 points, n = 25) LIPI risk (p = 0.171). One-year PFS estimates were 36%, 27%, and 10% (log-rank p = 0.015), and corresponding 1-year OS estimates were 53%, 52%, and 20% (log-rank p = 0.003), respectively. During ICI treatment, 1,227 LIPI measurements were available. In linear mixed modeling, the LIPI remained stable over time in the 29 patients without disease progression (average change/month=0.0 points, 95%CI: -0.1-0.0, p = 0.161), but increased over time in the 56 patients who developed disease progression (average change/month=0.02 points, 95%CI: 0.0-0.03, p = 0.004). Conclusions This study externally validated an elevated LIPI as a biomarker for poor ICI treatment outcomes in patients with advanced NSCLC. The LIPI increases before disease progression (Table). Continuous data are reported as medians [25th-75th percentile], and count data as absolute frequencies (%). Table . 1263P Baseline characteristics of the study population Variable Median IQR or absolute count % dNLR (units) 2.7 [1.8-4.1] LDH (U/L) 267 [199-346] Age (years) 67 [59-74] Female sex 41 (47%) ECOG performance status (points) 0 [0-1] Never smoker 19 (22%) Tumor histology / ---Squamous NSCLC 19 (22%) ---Adenocarcinoma 59 (68%) ---Other 9 (10%) PD-L1 expression (%) 50 [1-80] Treatment line of IO agent / ---1st line 36 (41%) ---2nd line 43 (49%) ---3rd, 4th, or 5th line 8 (10%) IO agent / ---Nivolumab 49 (56%) ---Pembrolizumab 35 (40%) ---Atezolizumab 3 (3%) Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.