Plasma IL-6 changes correlate to PD-1 inhibitor responses in NSCLC

• Published in: Journal for immunotherapy of cancer Vol. 8; no. 2; p. e000678
• Main Authors: Keegan, Alissa, Ricciuti, Biagio, Garden, Padric, Cohen, Limor, Nishihara, Reiko, Adeni, Anika, Paweletz, Cloud, Supplee, Julianna, Jänne, Pasi A, Severgnini, Mariano, Awad, Mark M, Walt, David R
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group LTD 01-10-2020; BMJ Publishing Group
• Series: Original research
• Subjects: Apoptosis; Biological variation; Biomarkers; Cancer; Cytokines; Gene expression; Immunology; Immunotherapy; Immunotherapy Biomarkers; Laboratories; Ligands; Lung cancer; Mutation; Plasma; Proteins; cytokines; lung neoplasms; immunotherapy; biomarkers, tumor
• ISSN: 2051-1426; 2051-1426
• DOI: 10.1136/jitc-2020-000678

BackgroundBlood-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.MethodsWe 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.ResultsA 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.ConclusionsThis study suggests the presence of a systemic, proteomic reflection of successful ICB outside the tumor microenvironment with plasma decreases in IL-6 and CRP.