Longitudinal Multiplex Cytokine Analysis For Patients (Pts) With Metastatic Renalcell Carcinoma (Mrcc) Treated With Ipilimumab/Nivolumab (I Plus N).

731 Background: I+N is an established treatment for mRCC, where circulating protein biomarkers are prognostic. In a longitudinal correlative study, we characterized circulating proteins in mRCC pts treated with standard of care I+N. Methods: mRCC pts treated with I+N were prospectively enrolled at Duke Cancer Institute (NCT02978118), contributing EDTA plasma at baseline, week(wk)-4, wk-12, and disease progression. Best overall responses were characterized as disease control (DC; stable disease, partial & complete responses) versus progressive disease (PD). Plasma was batch analyzed using a 46-plex MesoScale Discovery ELISA assay (IFN-g, interleukins [IL]-1b, 2, 4, 5, 6, 7, 8, 10, 12, IL-12-IL-23p40, 13, 15, 16, 17A, 21, 22, 27, 31, MIP-3a, Eotaxin, Eotaxin-3, IP-10, MCP-1&4, MDC, MIP-1a & 1b, TARC, TNF-a & b, GM-CSF, CRP, ICAM-1, SAA, VCAM-1, FGFb, FLT-1, PlGF, Tie-2, VEGF, VEGF-, and VEGF-D). Mean and standard deviations of cytokine concentrations are reported, along with a Wilcoxon rank sum test between PD and DC groups; unadjusted p-values are nominal. Results: We enrolled 25 pts with mRCC (15 DC and 10 PD). Baseline IL-7, IL-8, IL-12-IL-23p40, ICAM-1, TNF-a, VEGF-C, and VEGF-D were lower in PD pts than DC pts (Table). MIP-1b was significantly lower for PD than DC pts at baseline (Table) and wk-4 change (PD 0.30 +/- 1.82, DC 0.83 +/- 6.49, p = 0.056). Although baseline IFN-g did not differ between groups, wk-4 IFN-g significantly increased in DC and decreased in PD pts (DC 3.5 +/- 7.1; PD -1.33 +/- 5.47, p = 0.056). Conclusions: In this pilot exploratory analysis, a subset of ILs are higher at baseline in DC than PD pts. A wk-4 increase in circulating IFN-g is associated with DC vs PD and could be linked to increased early inflammation and response to I+N. Larger prospective studies are needed to validate these findings.[Table: see text]