Baseline circulating myeloid-derived suppressor cells subpopulations, neutrophils/lymphocytes ratio, and response to PD-1/PD-L1 inhibitor in non-small cell lung cancer patients.

Abstract

e15042 Background: Inhibitors of immune checkpoint PD-1/PD-L1 (ICI) have become a care standard in non-small cell lung cancer (NSCLC). Despite promising results, some patients cannot take advantage of immunotherapy effects. Nowadays, neither predictive nor prognostic circulating biomarkers have been found in order to select patients or to predict response to ICI. Myeloid-derived suppressor cells (MDSC) are potent immunity suppressors and may represent both a potential prognostic and a predictive biomarker. We aimed to assess the role of pretreatment circulating MDSC subpopulations on ICI outcomes in NSCLC patients. Methods: 86 NSCLC patients treated with ICI and 10 healthy donors in 3 centers between 02/2018 and 10/2019 were eligible. Pretreatment immunophenotyping of monocytes, early-MDSC (e-MDSC: CD14-/CD15-/HLA-DR-/CD33+/CD11b+), monocytic-MDSC (M-MDSC: CD14+/CD15-/HLA-DR-/CD33+/CD11b+) and polymorphonuclear-MDSC (PMN-MDSC: CD14-/CD15+/HLA-DR-/CD33+/CD11b+) was prospectively performed by flow cytometry in fresh whole blood. Correlation between baseline circulating MDSC subpopulations and Neutrophils/Lymphocytes Ratio (NLR) was evaluated as well as their impact on outcomes. Results: 86 patients who received at least one previous platinum based combination chemotherapy for stage III-IV NSCLC were prospectively included; 82 (95%) smokers, median age 62 years; 52 (60%) non-squamous; 69 (93%) ECOG PS 0-1; 43 (50%) PDL1 ≥ 1% and 65 (76%) were treated in a second line setting. Median PFS (mPFS) was 2.79 months (m) [95% CI, 1.3-4.2] and mOS 11.6 m [9.3-13.9]. Overall, 3m-death rate was 18.6%. Pretreatment high-NLR (NLR > 3) (62/86; 72%) was correlated with poor PFS (p = 0.03), OS (p = 0.01) and a 3m-death rate of 22.6%. High level of global MDSC before anti-PD-1/PD-L1 therapy, defined by the median value as a cut-off ( > 6.3%), was associated with poor OS (p = 0.03). Pretreatment low e-MDSC ( < 21.7%), were also associated with poor PFS (p = 0.01), OS (p = 0.006) and a 3m-death rate of 23.8%. There was not correlation between M-MDSC and PMN-MDSC and clinical outcomes. Conclusions: Our study suggests that a baseline circulating low level of e-MDSC and high-NLR are associated with early failure to ICI and poorer survival. The role of e-MDSC appears interesting as a potential predictive and prognostic biomarker in NSCLC patients treated with anti-PD1/PD-L1. Dynamic assessment of MDSC levels over time and further validation with longer follow up in larger cohorts are needed.