Baseline blood immune profiling to predict response to antiPD-1 in patients with advanced non-small cell lung cancer

Background: Immune checkpoint inhibitors have remarkably improved the natural history of patients (pts) with non-small cell lung cancer (NSCLC), with improved clinical responses and overall survival compared to standard therapy. However, over 80% of unselected NSCLC pts do not respond, highlighting the need of theranostic biomarker discovery. In a cohort of NCSLC pts treated with antiPD-1, we investigated blood immune parameters at baseline and pts characteristics as potential theranostic biomarkers. Methods: Thirty-four pts with locally advanced/metastatic NSCLC received antiPD-1 therapy as ≥ 2 line treatment in a prospective biomarker study (NCT02866149). Peripheral blood mononuclear cells and plasma were analyzed at baseline by multiparametric flow cytometry and Luminex technology, respectively. Primary endpoint was to correlate cellular and soluble immune parameters with clinical outcome based on RECIST criteria. Results: Baseline CD3+/CD14+ ratio was a robust predictive biomarker with pts achieving progression free survival (PFS) ≥4 months showing an average ratio of 1.91 vs 1.11 in pts with PFS <4 months (p = 0.003). Furthermore, we found a strong positive correlation between the proportion of HLA-DRhiCD14+ monocytes and the PFS (r = 0.471), with objective responders showing higher CD86 expression, suggesting an improved antigen-presenting capacity. In addition, pts with a PFS ≥4 months, displayed higher proportions of CCR7-CD45RA- effector memory CD8+T cells and regulatory CD4+T cells suggesting pre-existing adaptive immune responses. In line with previous reports, our results confirmed the association of baseline plasma albumin with clinical outcome, with levels ≥ 3.9 g/dL associated with improved PFS (p = 0.026), likely due to the lower plasma levels of the pro-inflammatory mediator IL-6. Finally, soluble CD40 ligand was elevated in pts with reduced PFS, probably in relation with an elevated platelet activation, further supported by a 2-fold increase in plasma concentration of baseline platelet-derived growth factors (PDGFs) in these pts. Conclusions: Our study identifies promising, predictive, immune-related biomarkers in NSCLC pts treated with PD-1 blockade. Clinical trial identification: NCT02866149. Legal entity responsible for the study: Institut Curie. Funding: Institut Curie. Disclosure: All authors have declared no conflicts of interest.