The Lung Immune Prognostic Index (LIPI), a predictive score for immune checkpoint inhibitors in advanced non-small cell lung cancer (NSCLC) patients

Abstract

Background: Derived NLR (neutrophils/(leucocytes-neutrophils) ratio) and lactate dehydrogenase (LDH) have been correlated to immune checkpoint inhibitors (ICI) benefit in melanoma. We tested whether baseline dNLR and LDH, as a score, could have the same role in advanced NSCLC patients. Methods: Baseline dNLR and LDH were retrospectively collected in 466 patients treated with ICI from Nov. 2013 to Jan. 2017, in a training cohort (N=161) and a validation cohort (N=305) from 8 European centers. As a control, a cohort (N=162) treated only with chemotherapy between Nov. 2012 and Jul. 2016 from 2 centers. The primary endpoint was overall survival (OS), and secondary endpoints were progression free survival (PFS) and disease control rate (DCR). Results: In the immunotherapy cohort, 301 patients (65%) were males, 422 (90%) smokers and 401 (87%) with PS ≥1, with median age 63 years; 270 (58%) had adenocarcinoma and 159 (34%) squamous; 85 (18%) were KRASmut, 19 (4%) EGFRmut and 6 (1%) ALK positive. PDL1 was ≥ 1% by immunohistochemistry in 96 (74%), negative in 33 (26%) and unknown in 337 patients. The median of prior lines was 1 (0- 11). In the training cohort, the median PFS and OS were 3months (m) [2-4] and 10m [8-13]. dNLR>3 and LDH> Upper Limit of Normal (ULN) were independent factors for OS (HR 2.22, 95% CI 1.23-4.01; HR 2,51, 1.32-4.76, respectively). According to dNLR>3 and LDH>ULN, LIPI categorized 3 groups (good: 0 factor, intermediate: 1 factor, poor: 2 factors), which correlated with outcome in both cohorts. Median OS for good, intermediate, and poor was 34m, 10m and 3m, respectively (p=0.0001). The PFS and DCR were also correlated (p=0.001, p=0.005). Same results were observed in the validation cohort for OS (p=0.004), PFS and DCR (both p=0.005), but not in the chemotherapy cohort for both factors analyzed. Conclusions: Baseline LIPI, combining dNLR>3 and LDH>ULN, predicts the resistance to ICI acording to OS, PFS and DCR, but it is not correlated with the efficacy of chemotherapy, suggesting LIPI as a predictive score in ICI treatment.