Circulating tumor cell (CTC) PD-L1 and interferon regulatory factor-1 (IRF-1) expression as biomarkers of anti-PD-(L)1 response.

Abstract

e14032 Background: Anti-PD-(L)1 checkpoint inhibitors (CPI) are remarkable due to durable responses, tolerability, and improvements in survival across multiple solid tumors. Unfortunately, CPI produce objective responses in only a small subset of solid tumors patients (pts). We hypothesized that PD-L1 and IRF-1 expression on CTC may correlate with CPI response, and evaluate their expression in this pilot study. Methods: Pts with metastatic solid tumors initiating anti-PD(L)-1 mono- or combination therapy were eligible. Pts had 7.5 cc of blood drawn for CTC evaluation at 3 timepoints: baseline, after 1 CPI dose, and 3-6 months after starting CPI or at time of CPI discontinuation. Peripheral blood CTC were isolated with the AccuCyte kit and stained for CK/EpCAM, anti-CD45, nuclear dye, PD-L1, and IRF-1. CTCs were then identified with CyteFinder software. Results: 16 pts have enrolled to date with median age 71 years (range 28-83) and median ECOG = 1 (range 0-3). 50% were female. Diagnoses include NSCLC (50%), head and neck cancer (13%), breast cancer (13%), and others (24%). CTC were identified at baseline in 13/16 pts (# CTCs range 0-101). 12 pts with baseline CTC have had restaging scans since starting CPI. By RECIST 1.1, 3 pts had partial response (PR), 1 had stable disease (SD), and 8 had progressive disease (PD). The pts with PR more frequently had IRF-1 staining on baseline CTC (Table), and 1/3 had PD-L1 staining. 6 pts had tumor PD-L1 staining available for correlation, and 3/6 of those pts were PD-L1+ (tissue PD-L1 ≥ 1%). 1/3 pts with PD-L1+ tumor staining had CTCs that were PD-L1+. In the 3 pts with negative PD-L1 tumor staining, 1 pt had a mixed PD-L1+/PD-L1- CTC population and the others had no PD-L1 staining. Conclusions: CTC isolation and enumeration seem feasible across tumor types. Pts with PR to anti-PD-(L)1/ might have higher prevalence of IRF-1+ CTC; however, results are preliminary and more pts and samples are being evaluated. [Table: see text]