TY - JOUR T1 - Plasma IL-6 changes correlate to PD-1 inhibitor responses in NSCLC JF - Journal for ImmunoTherapy of Cancer JO - J Immunother Cancer DO - 10.1136/jitc-2020-000678 VL - 8 IS - 2 SP - e000678 AU - Alissa Keegan AU - Biagio Ricciuti AU - Padric Garden AU - Limor Cohen AU - Reiko Nishihara AU - Anika Adeni AU - Cloud Paweletz AU - Julianna Supplee AU - Pasi A Jänne AU - Mariano Severgnini AU - Mark M Awad AU - David R Walt Y1 - 2020/10/01 UR - http://jitc.bmj.com/content/8/2/e000678.abstract N2 - Background Blood-based biomarkers of anti-solid tumor immune checkpoint blockade (ICB) response are lacking. We hypothesized that changes in systemic cytokine levels with the initial doses of programmed cell death protein 1 (PD-1) pathway inhibitors would correlate with clinical responses. New ultrasensitive ELISA technology enables quantitation of plasma proteins in sub-picogram-per-milliliter concentrations.Methods We measured plasma cytokines by ultrasensitive single-molecule array assays in patients with non-small-cell lung carcinoma before and during treatment with anti-PD-1 therapy. Association with best overall response and progression-free survival (PFS) was assessed by Kruskall-Wallis test and Kaplan-Meier plots with log-rank test, respectively.Results A decrease in interleukin 6 (IL-6) levels was associated with improved PFS (n=47 patients, median PFS: 11 vs 4 months, HR 0.45 (95% CI 0.23 to 0.89), p=0.04). The extent of change in IL-6 differed between best overall response categories (p=0.01) and correlated with changes in C reactive protein levels. We also explored plasma cytokine levels in relation to immune-related adverse effects and observed some correlation.Conclusions This study suggests the presence of a systemic, proteomic reflection of successful ICB outside the tumor microenvironment with plasma decreases in IL-6 and CRP. ER -