P2.01-044 Baseline Peripheral Blood Cell Subsets Associated with Survival Outcomes in Advanced NSCLC Treated with Nivolumab in Second-Line Setting: Topic: Immune Mechanisms in Thoracic Cancer and Targeted Therapy

Nivolumab is the first checkpoint inhibitor approved for the treatment of Squamous (Sq) and non-Squamous (non-Sq) metastatic NSCLC in second-line setting, showing a survival benefit in randomized phase III trials. The aim of this study is to investigate the potential role of baseline peripheral blood cells in relation to clinical outcomes following nivolumab treatment. From November 2015 to to June 2016, we evaluated 45 patients with Sq (n = 10) and non-Sq (n = 35) NSCLC, previously treated with first-line platinum-based chemotherapy, that received nivolumab 3 mg/kg IV on day 1 of each 2 week treatment cycle. Clinical characteristics (T-Stage, lymph nodes involvement, M-Stage) were assessed. Total numbers of leukocytes, myeloid-derived suppressor cells (MDSCs), including both monocytic (Mo-MDSC) and granulocytic (Gr-MDSC) type, regulatory T cells (T-regs), and serum lactate dehydrogenase (LDH) were assessed. Endpoints were correlation with objective response (OR), progression-free survival (PFS, categorized as ≤ 3 or > 3 months) and overall survival (OS). Tumor response was assessed using RECIST criteria, version 1.1, at week 9 and every 6 weeks thereafter until disease progression. Statistical methods were based on univariate analyses (Wilcoxon rank test). The median PFS of the overall study population was 3 months. Data about Gr-MDSCs (identified by flow cytometry as Lin-CD15+CD14-CD11b+HLA-DRlow/-), Mo-MDSCs (Lin-CD14-CD11b+HLA-DRlow/-) and absolute eosinophil counts (AEC) were available in 37/45 patients (82%) of treated patients. Baseline absolute numbers of Gr-MDSCs, Mo-MDSCs and AEC were greater in patients with good prognosis (PFS > 3 months) and better outcomes. In particular among patients with shorter PFS, the median numbers of Gr-MDSCs, Mo-MDSCs and AEC were significantly lower than those detected in patients with longer PFS (4 vs 13 cell/μl, p=0.01; 4 vs 21 cell/μl, p=0.06; 55 vs 155 cell/μl; p=0.02, respectively). No correlation was observed between T-regs, LDH, absolute neutrophil, monocyte, lymphocyte counts and clinical outcomes. A baseline blood signature characterized by low levels of Gr-MDSCs, Mo-MDSCs and AEC is associated with poor outcome (median PFS ≤ of 3 months) in 67.6% of patients treated with nivolumab. In contrast, patients (32.4%) with high levels of these three biomarkers showed a median PFS significant longer than 3 months. Overall survival analysis is ongoing.