Monitoring PD-L1 expression on circulating stromal cells in blood predicts PFS and OS in patients with metastatic NSCLC treated with PD-L1/PD-1 immunotherapy.

Abstract

8535 Background: Cancer Associated Macrophage Like cells (CAMLs), a circulating stromal cell found in cancer patients (pts) blood, are phagocytic giant macrophages that appear to parallel the inflammatory PD-L1 state of the tumor microenvironment. Previously, we demonstrated in local non-small cell lung carcinoma (NSCLC), CAML PD-L1 expression is dynamic and predicts response to PD-L1/PD-1 immunotherapies (IMTs) following sequential sampling before and after chemotherapy (chemo) induction (̃30days) based on progression free (PFS) & overall survival (OS). However this has not been tested in metastatic NSCLC (mNSCLC). Here,we report the results of monitoring PD-L1 expression in CAMLs before and after chemo induction (̃30 days) to evaluate its predictive value in mNSCLC pts treated with or without IMT. Methods: A single blind multi-year prospective study was undertaken to test the relationship of PD-L1 expression in CAMLs to PFS & OS, pre & post chemo induction, in recurrent mNSCLC with (n = 41) or without (n = 41) additional anti-PD-L1/PD-1 IMTs. This included three IMTs: atezolizumab (n = 4), nivolumab (n = 8) or pembrolizumab (n = 29). We recruited 82 pts with pathologically confirmed recurrent mNSCLC prior to treatment for newly recurrent metastatic disease. Blood samples (15 mL) were taken at Baseline (BL), prior to chemo, and ̃30 days after chemotherapy (T1). Blood was filtered by CellSieve filtration & CAMLs’ expression scored as a binary high/low, to evaluate PFS & OS hazard ratios (HRs) by censored univariate & multivariate analysis at 18 months. Results: CAMLs were found in 97% of all tested samples, 94% at BL & 100% at T1. CAML PD-L1 at BL was found not to be associated with PFS or OS in pts treated with chemo alone (PFS p = 0.620 & OS p = 0.673) or chemo+IMT (PFS p = 0.353 & OS = 0.477) at 18 months. At T1, high CAML PD-L1 in pts treated with chemo alone had no significantly different PFS (HR = 1.3, p = 0.694) or OS (HR = 1.6 p = 0.503). However, high CAML PD-L1 at T1 in pts treated with chemo+IMT had significantly better PFS (HR = 3.1, 95%CI = 1.3-7.3, p = 0.019), and OS (HR = 3.4, 95%CI = 1.4-8.3, p = 0.014). Further subtyping & analysis is ongoing to evaluate PFS and OS at 24 months. Conclusions: Our data suggests that in mNSCLC, PD-L1 expression in circulating CAMLs dynamically upregulates after induction with chemotherapy and appears to predict patients with increased benefit to PD-L1/PD-1 IMTs, though additional studies are needed to validate these findings.