Plasma Biomarkers Screening by Multiplex ELISA Assay in Patients with Advanced Non-Small Cell Lung Cancer Treated with Immune Checkpoint Inhibitors

SIMPLE SUMMARY: There is an unmet need for new predictive biomarkers associated with efficacy and immune-related toxicity of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC). In this study, we performed multiplex ELISA screening in plasma from 35 consecutive patients with advanced NSCLC treated with nivolumab or pembrolizumab, allowing large-scale screening for 48 cytokines involved in immune response and tumour proliferation. We found an association between ICIs efficacy and three cytokines: soluble hepatocyte growth factor (sHGF), soluble Fibroblast Growth Factor (sFGF) and interleukine-12 (IL-12). Moreover, TNF-α, IL-16, IL-12p40 and MCP3 were candidate biomarkers for predicting grade 3–4 immune-related toxicity. This exploratory study shows the potential role of new plasma biomarkers in advanced NSCLC treated with ICIs. ABSTRACT: Immune checkpoint inhibitors (ICIs) are commonly used in patients with advanced non-small cell lung cancer (NSCLC). An unmet need remains for new biomarkers associated with ICIs. In this study, consecutive patients with advanced NSCLC treated with nivolumab or pembrolizumab were included. Plasma at ICIs initiation was prospectively collected and a multiplex ELISA assay testing 48 cytokines and growth factors was performed. Exploratory endpoints were the association between plasma biomarkers with outcome and grade III–IV immune related adverse events (irAEs). Thirty-five patients were included. Patients without clinical benefit (n = 22) had higher pre-ICI soluble Hepatocyte Growth Factor (sHGF) (210.9 vs. 155.8 pg/mL, p = 0.010), lower pre-ICI soluble Fibroblast Growth Factor (sFGF) (4.0 vs. 4.8 pg/mL, p = 0.043) and lower pre-ICI interleukine-12 (IL-12) (1.3 vs. 2.2 pg/mL, p = 0.043) concentrations. Patients with early progression (n = 23) had higher pre-ICIs sHGF (206.2 vs. 155.8 pg/mL, p = 0.025) concentrations. Patients with low sHGF levels at ICIs initiation had longer progression-free survival and overall survival than those with high sHGF levels: respectively 2.5 vs. 8.0 months (p = 0.002), and 5.5 vs. 35.0 months (p = 0.001). TNF-α, IL-16, IL-12p40 and MCP3 were associated with high grade irAEs. This study shows the potential association between several plasma biomarkers with outcome and grade 3–4 IrAEs in advanced NSCLC treated with ICIs.