Abstract PS2-09-25: Monitoring Upregulation of PD-L1 in Cancer Associated Macrophage-Like Cells in Blood Predicts Clinical Outcomes in Metastatic Cancer Patients Treated with PD-L1 Immunotherapies

Abstract Background Numerous studies have shown the efficacy of PD-L1/PD-1 based immunotherapies (IMT) for treating patients with metastatic Breast Cancer (MBC) when there is high expression of PD-L1 in their tumor cells and/or tumor immune cells. However, many patients with high PD-L1 tumors do not respond to IMT, and some patients with negative/low PD-L1 tumors may respond to IMTs. The poor correlations between IHC scores and IMT responses are often attributed to the dynamic nature of PD-L1 which may upregulate after chemotherapy, radiation, or other systemic therapies, which is not quantified by IHC tumor immunostaining. Recently, a number of clinical trials have described PD-L1 upregulation in giant phagocytic stromal macrophages found in circulation, i.e. Cancer associated macrophage-like cells (CAML), that may correlate with IMT responses in solid tumors. We conducted a prospective pilot study to monitor the peripheral blood of n=67 MBC patients undergoing systemic treatment with IMT in combination with other therapies, to evaluate CAML PD-L1 prior to and post IMT induction (∼47 days) with clinical outcome analysis at 2 years. Methods In a prospective pilot study of previously treated MBC patients n=67, all starting new lines of systemic therapy in combination with IMT (pembrolizumab [n=57], nivolumab [n=2], or atezolizumab [n=8]) with active progressive metastatic disease. Of the patients, median age was 58.2 (range: 32-73). Median prior lines of therapy in the metastatic setting was 2 (range 0-14). Race demographics (Caucasian=43, Black=7, Hispanic=4, Asian=3 & unknown/other=11). ECOG 0 (n=34) and ECOG 1 (n=33). Visceral metastasis (n=43) and non-visceral (n=24). ER positivity was 37% (n=25), PR positivity was 39% (n=26), HER2 positivity was 13% (n=9) and 52% were triple negative breast cancer (n=35). Histology was IDC (n=52), Other (n=11), ILC (n=2), & IBC (n=2). 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 (∼47 days) after IMT induction. Patient’s 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. Results Baseline T0 PD-L1 CAML data was available for 94% (n=63/67) of patients, with 44% (n=28/63) having high CAML PD-L1 which was not correlated with improved PFS (HR=1.3, 95%CI=0.7-2.3, p=0.5376) or OS (HR=1.3, 95%CI=0.7-2.5, p=0.5915). T1 PD-L1 CAML data was available for 78% (n=52/67) of patients, with 58% (n=30/52) having high CAML PD-L1 which significantly correlated with improved PFS (HR=3.1, 95%CI=1.3-7.2 p=0.0170,) and improved OS (HR=4.2, 95%CI=1.6-11.4, p=0.0102). 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)=2.2 months and median OS (mOS)=7.2 months. In contrast, patients who increased CAML PD-L1 after IMT induction had better responses, mPFS=6.3 months and mOS=13.1 months. Further, patients with consistently high PD-L1 at T0 & T1 had the best response rates, mPFS=9.5 months and mOS=19.7 months. Conclusion Here we describe a blood-based biopsy which can monitor dynamic PD-L1 changes in circulating tumor immune cells and may predict enhanced clinical benefit to PD-L1 IMTs in MBC. While an initial pilot study on a small population of patients, PD-L1 expression on CAMLs appears to identify patients with improved IMT responses and suggests larger validation studies are needed. Citation Format: D. L. Adams, M. Cristofanilli, C. Reduzzi, W. V. Williams, G. Del Priore, S. Chumsri, T. Iwase, N. T. Ueno, A. B. Duffy, C. Tang. Monitoring Upregulation of PD-L1 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 San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-09-25.