Sequential monitoring of circulating stromal cells from blood is predictive of progression in NSCLC patients undergoing anti-PD-L1 therapy after definitive chemoradiation therapy.

Abstract

3051 Background: Cancer Associated Macrophage-Like cells (CAMLs) are a recently described circulating stromal cell common in the peripheral blood of patients with solid tumors. In non-small cell lung carcinoma (NSCLC), patients with CAMLs ≥50µm after completion of chemoradiation therapy (CRT) have been shown to have worse progression free survival (PFS). However, with the recent addition of anti-PD-L1 therapies in conjunction with CRT as standard of care, it has never yet to be evaluated whether CAMLs remain predictive for monitoring progression in NSCLC patients post anti-PD-L1 therapy. Methods: A 2 year single blind prospective study was undertaken to test the relationship of ≥50µm CAMLs to PFS based on imaging in lung patients before and after induction of CRT and PD-L1. We recruited 104 patients with pathologically confirmed unresectable NSCLC Stage II (n = 14), Stage III (n = 83), Stage IV (n = 3), and locally recurrent disease (n = 4). Baseline (BL) blood samples were taken prior to start of therapy. A second time point blood sample (T1) was taken at the end of radiotherapy (~40 days). A third time blood sample (T2) was taken after induction of anti-PD-L1 therapy (e.g. Imfinizi, Keytruda, etc.). Blood was filtered by CellSieve filtration and CAMLs were quantified. Analysis by CAML size of < 49 µm or ≥50 µm was used to evaluate PFS hazard ratios (HRs) by censored univariate & multivariate analysis. Results: CAMLs were found in 87% of samples averaging 2.9 CAMLs/7.5mL sample. At BL, CAMLs ≥50 µm had similar PFS to patients with < 50 µm CAMLs (HR = 1.1 95%CI 0.6-1.95 p = 0.8661). However, after CRT (T1), patients with CAML size ≥50 µm had worse PFS (HR = 3.2, 95%CI 1.8-5.8 p = 0.0002). After induction of anti-PD-L1 therapy (T2), patients with ≥50 µm CAMLs also had worse PFS (HR = 2.8 95%CI 1.5-5.4 p = 0.0037). CAML size at BL was not accurate at predicting progression within 24 months; however ≥50 µm CAMLs after CRT or after 1 cycle of anti-PDL1 therapy was 71% accurate at predicting progression of disease. Conclusions: Our data suggests that in NSCLC, ≥50 µm CAMLs after completion of CRT or appearing after induction of anti-PD-L1 therapy appears to predict progressive disease. If validated, additional studies are needed to determine if CAMLs can serve as a significantly prognostic blood based marker for predicting survival in NSCLC patients early in the treatment regime.