Expression Of Pd-L1 On Circulating Stromal Cells Predicts Immunotherapy Response In Unresectable Non-Small Cell Lung Carcinoma After Definitive Chemoradiotherapy

Background: Circulating stromal cells (CStCs) have been found to be common in the peripheral blood of cancer patients and hypothesized to be a blood based biomarker for monitoring cancer treatment. It has previously been described that the dynamic changes of PD-L1 expression during chemoradiotherapy (CRT) could be tracked using circulating stromal cells. However, how these changes relate to PD-L1/PD-1 immunotherapy (IMT) response is unstudied. We prospectively monitored PD-L1 expression in 2 cell types found in circulation (Circulating Tumor Cells [CTCs] and Cancer Associated Macrophage-like Cells [CAMLs]) in locally advanced non-small cell lung cancer (NSCLC) patients (pts) treated with Atezolizumab (Atezo) after definitive CRT (n=39) or in pts with CRT alone (n=40). Methods: A 2 year single blind prospective study was undertaken in pts with locally advanced NSCLC in 40 patients treated with CRT alone, or from a phase II DETERRED trial (NCT02525757) where Atezo was added for 1 year after completing CRT (n=10), or concurrently and after CRT (n=30). Samples from 39 of 40 pts from the DETERRED study were available for analysis. Baseline blood samples (7.5 ml) were drawn prior to start of CRT (T0), and a second sample was drawn ~1 month after completing CRT (T1), but prior to induction of Atezo. Blood was processed by CellSieve™ microfilters; stained for cytokeratin/PDL1/CD45 to identify CTCs and CAMLs. PD-L1 intensity was measured and grouped by 4 scores: 0-negative, 1-low, 2-medium, \u0026 3-high. PD-L1 levels from circulating cells were used to evaluate PFS and OS. Significance was assessed by log-rank testing. Results: At least one CTC and/or CAML was found in 91% of available T0 samples and 96% of available T1 samples. In the 40 patients that received CRT alone, 35 pts had measurable cells at T0 and PD-L1 expression in CStCs was low (0-1) in 20 pts and high (2-3) in 15 pts. Further, at T1 PD-L1 expression in CStCs was low in 12 pts and high in 28 pts, with no relationship to PFS (T0 HR=1.1, 95%CI 0.5-2.8, p=0.96 and T1 HR=0.8, 95%CI 0.3-2.0, p=0.82) or OS (T0 HR=0.8, 95%CI 0.2-2.8, p=0.99 and T1 HR=1.1, 95%CI 0.3-3.5, p=0.84). In the patient arm that received Atezo at T0, PD-L1 expression in CStCs was low in 21 pts and high in 17 pts, with no relationship to PFS (HR=0.5, 95%CI 0.2-1.7, p=0.18) or OS (HR=1.6, 95%CI 0.4-6.0, p=0.75). However at T1, pts with high PD-L1 had significantly improved PFS response to Atezo (HR 5.4, 95%CI 1.7-17.0, p=0.009), and improved OS (HR 21.5, 95%CI 4.5-91.9, p Conclusions: PD-L1 expression in tissue is often not used in IMT treatment decisions due to limited correlation with clinical responses. However, it has been suggested that sequential monitoring of PD-L1 expression in circulating stromal cells in blood may predict for patients who will respond to IMT. These data suggests that CRT altered PD-L1 expression, and monitoring dynamic changes of PD-L1 in CStCs may predict immunotherapy effectiveness in NSCLC after CRT. Citation Format: Daniel L. Adams, Jianzhong He, Yawei Qiao, Kirby P. Gardner, John V. Haymach, Anne S. Tsao, Ashvathi Raghavakaimal, Cha-Mei Tang, Alexander Augustyn, Steven H. Lin. Expression of pd-l1 on circulating stromal cells predicts immunotherapy response in unresectable non-small cell lung carcinoma after definitive chemoradiotherapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3297.