Abstract 2061: Monitoring PD-L1 expression in cancer associated macrophage-like cells in blood predicts clinical outcomes in metastatic cancer patients treated with PD-L1 immunotherapies

Abstract Studies have described the efficacy of immunotherapies (IMT) utilizing programmed death 1 receptor and its ligand (PD-L1) for treating solid tumors. However, many patients (pts) fail to respond to IMT, underscoring the need for better predictive biomarkers for improved pt identification and stratification. Poor IMT responses are often attributed to the dynamic nature of PD-L1 which may change after chemotherapy or radiation and is quantified by static immunostaining. Recently, studies have described PD-L1 upregulation in giant phagocytic stromal cells, i.e. Cancer associated macrophage-like cells (CAML), circulating macrophages that have engulfed tumors before entering circulation and may predict IMT responses. We conducted a pilot study to monitor the peripheral blood of n=46 metastatic cancer pts undergoing systemic treatment with IMT in combination with other therapies, to evaluate CAML PD-L1 prior to and post IMT induction with clinical correlation at 2 years. In a prospective pilot study of n=46 metastatic cancer pts, breast (n=14), non-small cell lung (n=24), and renal cell (n=8), all starting new lines of systemic chemotherapy in combination with IMT (pembrolizumab [n=30], nivolumab [n=13], Durva [n=1], or atezolizumab [n=3]) for newly diagnosed recurrent metastasis (n=24) or with previously treated progressive metastatic disease (n=22). We isolated CAMLs from 7.5 ml baseline (T0) blood using the LifeTracDx® PD-L1 test and scored PD-L1 as high or low. If possible, a follow-up sample (T1) was taken (∼48 days) after IMT induction. Pts’ progressive free survival (PFS) and overall survival (OS) hazard ratios (HRs) were analyzed by censored univariate analysis based on RECIST v1.1 over 2 years. T0 PD-L1 CAML data was available for 89% (n=41/46) of pts, with 39% (n=16/41) having high CAML PD-L1 which was not correlated with improved PFS (HR=0.9, p=0.985, CI=0.5-1.9) or OS (HR=1.0, p=0.899, CI=0.4-2.2). T1 PD-L1 CAML data was available for 74% (n=34/46) of pts, with 53% (n=18/34) having high CAML PD-L1, which significantly correlated with improved PFS (HR=2.9, p=0.012, CI=1.3-6.4) and OS (HR=5.5, p=0.0005, CI=2.2-13.6). In comparing CAML PD-L1 change post IMT, it was found that consistently low PD-L1 at T0 & T1 had the poorest responses, median PFS (mPFS)=2.3 months and median OS (mOS)=5.5 months. In contrast, consistently high PD-L1 at T0 & T1 had better responses, mPFS=6.1 months and mOS=16.7 months. Further, pts who increased in CAML PD-L1 after IMT had the best response rates, mPFS=10.3 months and mOS=14.8 months. Here, we describe a cancer agnostic blood-based biopsy to monitor dynamic PD-L1 changes in circulating tumor immune cells and predict clinical benefit to PD-L1 IMTs in several cancer types. While this initial pilot study appears to stratify pts with better IMT responses, larger validation studies are needed. Citation Format: Dimpal M. Kasabwala, Steven H. Lin, Massimo Cristofanilli, Carolina Reduzzi, Cha-Mei Tang, Thai H. Ho H. Ho, Daniel L. Adams. Monitoring PD-L1 expression in cancer associated macrophage-like cells in blood predicts clinical outcomes in metastatic cancer patients treated with PD-L1 immunotherapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2061.