Abstract 2635: Baseline myeloid-derived suppressor cell and eosinophil cell counts predict clinical efficacy in patients with non-small cell lung cancer (NSCLC) treated with nivolumab in second line

The anti-PD-1 monoclonal antibody nivolumab is clinically active in a variety of tumor types including squamous (sq) and non-squamous (non-sq) NSCLC in second-line, where randomized phase III trials have shown a survival benefit. However, no predictive/prognostic or dynamic biomarkers have been foun...

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Veröffentlicht in:Cancer research (Chicago, Ill.) Ill.), 2017-07, Vol.77 (13_Supplement), p.2635-2635
Hauptverfasser: Mancuso, Patrizia, Passaro, Antonio, Labanca, Valentina, Gandini, Sara, Spitaleri, Gianluca, Guerini, Elena, Barberis, Massimo, Noberasco, Cristina, Signore, Ester del, Pochesci, Alessia, Catania, Chiara, Marinis, Filippo De, Bertolini, Francesco
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Sprache:eng
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Zusammenfassung:The anti-PD-1 monoclonal antibody nivolumab is clinically active in a variety of tumor types including squamous (sq) and non-squamous (non-sq) NSCLC in second-line, where randomized phase III trials have shown a survival benefit. However, no predictive/prognostic or dynamic biomarkers have been found so far to correlate with clinical benefit in patients treated with anti-PD-1 antibodies. The aim of the present study is to investigate the potential role of baseline peripheral blood cell counts in relation to survival and response rate in NSCLC patients treated with nivolumab in a second-line setting. From July to May 2016 we evaluated 45 patients with Sq (n = 10) and non-Sq (n = 35) NSCLC, previously treated with first-line platinum-based chemotherapy, who 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 white blood cells, myeloid-derived suppressor cells (MDSCs, including both monocytic [Mo-MDSC]) and polymorphonuclear [PMN-MDSC] types), regulatory T cells (T-regs), and serum lactate dehydrogenase (LDH) were assessed. Endpoints were correlations with objective response rate (RR), 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 investigations were based on univariate analyses by the Wilcoxon rank test. The median PFS of the overall study population was 3 months. Data about PMN-MDSCs (identified by flow cytometry as Lin-CD15+CD14-CD11b+HLA-DRlow/-), Mo-MDSCs (Lin-CD14-CD11b+HLA-DRlow/-) and absolute eosinophil count (AEC) were available in 37/45 patients (82% of treated patients). Baseline absolute numbers of PMN-MDSCs, Mo-MDSCs and AEC were greater in patients with a good prognosis (PFS > 3 months) and a better RR. In particular, among patients with shorter PFS and lower RR, the median numbers of PMN-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). Our data suggest that a baseline blood signature characterized by low levels of PMN-MDSCs, Mo-MDSCs and AEC is associated with a poor clinical outcome (median PFS ≤ of 3 months and low RR) in 67.6% of patients treated with nivolumab. In contrast, patients with high level
ISSN:0008-5472
1538-7445
DOI:10.1158/1538-7445.AM2017-2635