Giant Circulating Cancer-Associated Macrophage-Like Cells are Associated with Disease Recurrence and Survival in Non-Small Cell Lung Cancer Treated with Chemoradiation and Atezolizumab

ABSTRACT PURPOSE Cancer-associated macrophage-like cells (CAMLs) are a potential peripheral blood biomarker for disease progression. This study used data from a phase 2 clinical trial to evaluate prognostic utility of CAMLs for locally advanced non-small cell lung cancer (NSCLC) treated with definitive chemoradiotherapy (CRT) and atezolizumab (DETERRED; NCT02525757). EXPERIMENTAL DESIGN Sample collection occurred at baseline (T0), during CRT (T1), end of CRT (T2), and at first follow up (T3). CAMLs were captured and quantified by the CellSieve™ system using multiplex immunostaining. “Giant” CAMLs were defined as characteristic CAMLs ≥ 50 μm. Kaplan-Meier methodology estimated progression-free survival (PFS), distant failure-free survival (DFFS), relapse-free survival (RFS) and overall survival (OS) at 30 months. RESULTS Thirty-nine patients were evaluated between December 2015 and March 2018. Median follow-up was 27 months. Most patients were stage III (85%) and had squamous cell (38%) or adenocarcinoma (59%). In total, 267 blood samples were analyzed. Giant CAMLs were identified in 57%, 60%, 64%, and 63% of patients at T0, T1, T2, and T3, respectively. Patients with giant CAMLs at T3, occurring at a median of 30 days after completion of CRT, had significantly worse DFFS (HR 4.9, p = 0.015), PFS (HR 2.5, p = 0.025), RFS (HR 2.4, p=0.036), and OS (HR 3.5, p=0.034) compared to patients with small or no CAMLs. CONCLUSIONS Presence of giant CAMLs after CRT completion was associated with development of metastatic disease and poorer survival despite the use of maintenance immunotherapy. Monitoring CAMLs may help risk stratify patients for adaptive treatment strategies.