Monitoring PD-L1 positive circulating tumor cells in non-small cell lung cancer patients treated with the PD-1 inhibitor Nivolumab

TLDR

PD‑L1 status in lung tumor tissue has an inconclusive predictive value for response to immune checkpoint inhibitors. The study aims to evaluate liquid biopsy for real‑time monitoring of PD‑L1 in patients. Twenty‑four stage IV NSCLC patients treated with Nivolumab were monitored by CellSearch for PD‑L1‑positive circulating tumor cells at baseline, 3 and 6 months to correlate with clinical outcomes. Baseline and 3‑month PD‑L1‑positive CTCs predicted poor outcome, but at 6 months only PD‑L1‑negative CTCs were associated with benefit while PD‑L1‑positive CTCs predicted progression, indicating persistent PD‑L1‑positive CTCs may signal therapy escape.

Abstract

Abstract Controversial results on the predictive value of programmed death ligand 1 (PD-L1) status in lung tumor tissue for response to immune checkpoint inhibitors do not allow for any conclusive consideration. Liquid biopsy might allow real-time sampling of patients for PD-L1 through the course of the disease. Twenty-four stage IV NSCLC patients included in the Expanded Access Program with Nivolumab were enrolled. Circulating tumor cells (CTCs) were analyzed by CellSearch with anti-human B7-H1/PD-L1 PE-conjugated antibody. PD-L1 expressing CTCs were assessed at baseline, at 3 and 6 months after starting therapy, and correlated with outcome. At baseline and at 3 months of treatment, the presence of CTCs and the expression of PD-L1 on their surface were found associated to poor patients outcome. Nevertheless, the high frequency of PD-L1 expressing CTCs hampered to discriminate the role of PD-L1 in defining prognosis. Conversely although CTCs were found in all patients 6 months after treatment, at this time patients could be dichotomized into two groups based PD-L1 expression on CTCs. Patients with PD-L1 negative CTCs all obtained a clinical benefit, while patients with PD-L1 (+) CTCs all experienced progressive disease. This suggests that the persistence of PD-L1(+) CTCs might mirror a mechanism of therapy escape.