Evaluation of baseline circulating eMDSCs in patients with advanced non–small cell lung cancer treated with first-line immunotherapy-based treatment.

Abstract

e20616 Background: Early myeloid-derived suppressor cells (eMDSCs) are implicated in tumor-driven immune dysregulation, but their prognostic role in patients with advanced non-small cell lung cancer (NSCLC) treated with immunotherapy-based regimens remains unclear. Methods: Patients with advanced-stage NSCLC eligible for immunotherapy (IO)-based treatment according to programmed death-ligand 1 (PD-L1) expression were prospectively enrolled within the APOLLO11 trial at the Istituto Nazionale dei Tumori of Milan. Clinical and pathological characteristics were collected through the REDCap platform. Baseline circulating eMDSCs were quantified by flow cytometry and defined as CD11b⁺CD33⁺CD15⁻ cells within the Lin⁻HLA-DR⁻ peripheral blood mononuclear cells. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Optimal cut-offs for eMDSC levels were defined using both objective response rate (ORR)-based and survival-optimized (MaxStat) approaches. Cox proportional hazards models were used to assess the prognostic impact of eMDSCs and to test interactions with treatment type. Results: Among 84 patients, 31 (36.9%) were female, and the mean age of the overall cohort was 70.1 years. Most patients were current or former smokers (95.2%) and had adenocarcinoma histology (75.0%). First-line chemo-IO was administered in 70 patients (83.3%), while 14 (16.7%) received IO alone. Median follow-up was 20.5 months (95% CI 18.3–24.4), median OS was 13.5 months (95% CI 9.9–not reached), and median PFS was 5.0 months (95% CI 4.5–6.4). Baseline eMDSC levels were low and right-skewed (median 0.38%, IQR 0.12–1.33). Using a MaxStat-derived cut-off (0,42%), median PFS differed according to eMDSC levels (5.2 vs 2.7 months), with a higher risk of progression observed in patients with low eMDSC levels (HR 1.9, p < 0.05). Similar results (PFS 5.2 vs 2.8 months) were observed using an ORR-derived cut-off (0,044%). Low eMDSC levels remained associated with shorter PFS after adjustment for treatment (p = 0.023) and histology (p = 0.024), while the association was attenuated (p = 0.14) after adjustment for performance status (PS). PS showed a strong independent prognostic impact (p < 0.001). Conclusions: Low baseline circulating eMDSC levels were associated with shorter PFS in patients with advanced NSCLC treated with immunotherapy-based regimens; this association was independent of treatment type and histology but attenuated after adjustment for PS. These findings support a prognostic role for eMDSCs and highlight the complexity of myeloid immune regulation beyond peripheral blood measurements.