Predictive role of plasmatic biomarkers in advanced non-small cell lung cancer (NSCLC) treated with nivolumab (nivo).

Background: Nivolumab (nivo) is an anti-PD1 antibody, used in second line treatment in non-small cell lung cancer (NSCLC). We investigated the potential interest of immune-related blood markers in patients with advanced NSCLC treated with nivo. Patients and methods: Plasma samples of 43 consecutive patients were prospectively collected at the time of diagnosis of cancer, at the initiation of nivo and at the first tumour evaluation (2 months). Concentrations of soluble PD-L1 (sPD-L1), soluble PD-L2 (sPD-L2), Interleukine-2 (Il-2), Interferon-gamma (IFN-γ), and Granzyme B (GranB) were quantified by ELISA. Plasmatic miRNA screening was also performed at the initiation of nivo. Expression of PD-L1 on tumour biopsies was evaluated by immunohistochemistry (IHC) using E13LN. Tumour response was evaluated by iRECIST. Results: High sPD-L1 at 2 months and increase of sPD-L1 concentrations at the beginning of nivo treatment were associated with poor response and tumour progression within 6 months of treatment. sPD-L1 concentrations at diagnosis were not correlated with PD-L1 expression on corresponding tumour samples. Low GranB at nivo initiation was also associated with poor response. High sPD-L1 and low GranB were associated with poor progression-free survival (PFS) and overall survival (OS). Low sPD-L2, low Il-2 and high IFN-γ were associated with grade 3-4 toxicities. miRNA screening showed that patients with long-term clinical benefit (n=9) had down-expression of miRNA-320b and -375 compared to patients with early progression at 2 months (n=9). Conclusion: Our results showed the predictive value of circulating biomarkers in patients with NSCLC treated with nivo.