journal contribution
posted on 2023-04-01, 00:02 authored by Philippe Rochigneux, Aaron Lisberg, Alejandro Garcia, Samuel Granjeaud, Anne Madroszyk, Stéphane Fattori, Anthony Gonçalves, Raynier Devillier, Pauline Maby, Nassim Salem, Laurent Gorvel, Brice Chanez, Jaklin Gukasyan, James Carroll, Jonathan Goldman, Anne Sophie Chretien, Daniel Olive, Edward B. Garon Supplementary Figure 1: Graphical Abstract
Supplementary Figure 2: Overall Survival in NSCLC patients treated with pembrolizumab in KEYNOTE-001 according to EGFR mutation
Supplementary Figure 3: Recursive partitioning identified classical monocytes and NK as the main immune populations whose frequency splits patients into distinct patterns of overall survival
Supplementary Figure 4: Classical monocytes, NK cells and ICOS+ CD4+ T cells are associated with improved pembrolizumab efficacy in advanced NSCLC patients.
Supplementary Figure 5: Gating strategy of the 3 main immune populations associated with pembrolizumab efficacy.
Supplementary Figure 6: Comparison side by side of Maxstat cut-offs with cut-off from Younden index for overall survival in the 3 populations of interest.
Supplementary Figure 7: Survival outcomes in NSCLC patients treated with pembrolizumab in KEYNOTE-001 according to blood baseline frequency of classical monocytes.
Supplementary Figure 8: Baseline immune peripheral score is also associated with PFS in melanoma patients treated with PD-1 inhibitors.
Funding
Fondation de France (Foundation of France)
Philippe Foundation (PHILIPPE FOUNDATION INC)
Fondation pour la Recherche Médicale (FRM)
Fondation ARC pour la Recherche sur le Cancer (ARC)
Foundation for the National Institutes of Health (FNIH)
LUNGevity Foundation (LUNGevity)
History
ARTICLE ABSTRACT
Immune checkpoint inhibitors (ICI) have revolutionized the treatment of non–small cell lung cancer (NSCLC), but predictive biomarkers of their efficacy are imperfect. The primary objective is to evaluate circulating immune predictors of pembrolizumab efficacy in patients with advanced NSCLC.
We used high-dimensional mass cytometry (CyTOF) in baseline blood samples of patients with advanced NSCLC treated with pembrolizumab. CyTOF data were analyzed by machine-learning algorithms (Citrus, tSNE) and confirmed by manual gating followed by principal component analysis (between-group analysis).
We analyzed 27 patients from the seminal KEYNOTE-001 study (median follow-up of 60.6 months). We demonstrate that blood baseline frequencies of classical monocytes, natural killer (NK) cells, and ICOS+ CD4+ T cells are significantly associated with improved objective response rates, progression-free survival, and overall survival (OS). In addition, we report that a baseline immune peripheral score combining these three populations strongly predicts pembrolizumab efficacy (OS: HR = 0.25; 95% confidence interval = 0.12–0.51; P < 0.0001).
As this immune monitoring is easy in routine practice, we anticipate our findings may improve prediction of ICI benefit in patients with advanced NSCLC.
