164P Circulating cytokines levels as predictive biomarkers in pleural mesothelioma: Preliminary data from a prospective translational study

The difference in circulating cytokines levels between epithelioid (E) or non-epithelioid (NE) Pleural Mesothelioma (PM) and their modulation after chemotherapy (ChT) or immune checkpoint inhibitors (ICIs) have not yet been described. This prospective translational study included patients (pts) with E or NE PM treated respectively with ChT and ICIs. The primary aim was to explore the prognostic role of cytokines levels, their dynamic change during ChT or ICIs and their correlation with progression-free survival (PFS). Blood samples were collected at baseline (T0) and at the end of ChT cycles or at first radiological imaging during ICIs (T1). Plasma levels of IL-1b, IL-2, IL-6, IL-8, IL-10, MCP1, HGF, TGFb1, TNFa, GM-CSF were quantified by enzyme-linked immunosorbent assay. A combined score (CS) of IL-8, IL-6 and HGF levels was calculated. Thirty-two pts were included, 18 (56%) treated with platinum-pemetrexed and 14 (44%) with ipilimumab-nivolumab. At T0, higher levels of IL-1b (p=0.039), IL-6 (p=0.001), IL-8 (p=0.007), IL-10 (p=0.015), and TNFa (p=0.001) were observed in NE vs E PM pts; no differences were seen for MCP1, GM-CSF, HGF, TGFb1 and IL-2. A trend was observed between lower levels of IL-8 and longer PFS with ChT (p=0.070). Plasma levels of IL-8 increased with ChT (p=0.004) and decreased with ICIs (p=0.002). Lower levels of IL-6 correlated with better PFS after ChT (p=0.054); a similar trend was seen with ICIs (p=0.164). HGF levels were not related to PFS, but HGF decreased at T1 after ICIs (p=0.014). Lower levels of IL-10 correlated with longer PFS after ICIs (p=0.049); T0-T1 levels of IL-10 increased after ChT (p=0.001) and ICIs (p=0.006). Lower levels of the CS of IL-8, IL-6 and HGF correlated with longer PFS after ChT (p=0.026); a trend with ICIs was seen (p=0.062). A T0-T1 decrease of the CS was seen in ICIs group (p=0.004). No relation between cytokines levels and neutrophil to lymphocyte ratio, platelet to lymphocyte ratio and immune related adverse events was seen. In this series, circulating cytokines were differently expressed in E vs NE pts; some cytokines showed a prognostic and predictive role after ChT or ICIs. ICIs may have a key role in decreasing some cytokines levels.