Abstract

Tumor characteristics and host immune system play a crucial role for the immune response. As reported in preclinical studies, a sustain immune cell proliferation in the periphery is necessary for the immune response and tumor destruction. More evidence in melanoma patients (pts) and less evidence are available in non small cell lung cancer (NSCLC). Aim of this study is to demonstrate the role of the peripheral blood as biomarkers in NSCLC patients treated with checkpoint inhibitors (CPIs). 94 evaluable patients from one institution NSCLC pts, treated with at least one course immunotherapy (IO) (nivolumab and pembrolizumab) in 2nd or further line, were considered for analysis. Baseline peripheral blood, at week 2 and 4 were collected for each patients. Univariate analysis were performed and correlation between biomarkers and progression free-survival (PFS) and overall survival (OS) are reported. median age was 67 years (31-86 years), most pts were male (80%), 35 pts were S and 59 NS. 75,5% of pts were smokers and Eastern Cooperative Oncology Group (ECOG) pre-IO were: 0 (5,3%), 1 (58,5%) and 2 (36,2%). Overall median (m) PFS and mOS were 3,93 months (mo) and 20,7 mo respectively. Baseline absolute neutrophil count (ANC) ≥ 7500/μL and neutrophil to lymphocyte ratio (NLR) >5 correlate with worse PFS (3.3 mo vs 5.5 mo, p=0.04 and 2.8 mo vs 5.4 mo, p=0.006 respectively) and OS ( 15.6 mo vs 34.9 mo p=0.02 and 16.7 vs 34.9 mo p=0.004, respectively ). Poor OS and PFS were persist at week 2 in pts with NLR ≥5 (HR=0.3, p<0.0001 for OS and PFS), this was not significant at week 4. Also, baseline derived neutrophil to lymphocyte ratio (dNLR) >3 correlate with worse PFS ( p=0.01) and OS (p=0.016). Absolute lymphocyte count (ALC) ≥1000/μL at baseline and week 2 confer higher PFS (5.3 mo vs 3.1 mo, p=0.05) and a tred in OS. Interestingly, week-4 absolute monocytic count (AMC)≥ 1000/μL imply a poor PFS and this was not observed at baseline and week 2. Low, absolute eosinophil count (AEC) <50/ μL correlate with worse PFS (p=0.031). Finally, pts with lymphocyte monocyte ratio (LMR)≥ 1.5 at baseline, week 2 and 4 correlate with better survival. Despite the retrospective nature, in our knowledge, this is the first study to demonstrate the role of AMC in NSCLC pts. Also, LMR could probably reflect the peripheral immune-fitness. However, prospective sudies are needed to confirm their role.

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