Abstract P1-04-10: Peripheral blood cells as predictors of immune-related toxicity in early triple negative breast cancer (eTNBC)

Abstract Background: Immune Checkpoint Inhibitors (ICI) acquired an impactful role in high risk early triple negative breast cancer (eTNBC). In particular, KEYNOTE-522 study has demonstrated that the addition of pembrolizumab to neoadjuvant chemotherapy (NACT) improves pCR rate and survival outcomes. Therefore, this novel regimen is characterized by an enhanced and potentially irreversible toxicity profile. The identification of biomarkers able to predict immune-related adverse events (irAEs) is ongoing in different neoplasms. Recent evidence showed a potential emerging role of blood cell counts and ratios, such as lymphocytes and monocytes. With these premises, the aim of our study is to explore if peripheral blood biomarkers should predict irAEs in eTNBC patients candidate to receiving immunotherapy in peri-operative setting. Methods: The study enrolled 20 eTNBC patients undergoing NACT containing pembrolizumab. Patients were divided into two subgroups based on the development of irAEs; patients who experienced toxicity were selected depending on the immunotherapy's discontinuation. Patients performed blood samples at baseline before starting treatment and Flow Cytometry analysis was used to characterized monocytes, circulating T cells (CD3, CD4 and CD8) and Myeloid Derived Suppressor Cells (MDSCs). The statistical analysis was performed using Mann Whitney U Kruskal-Wallis (p<0.05) for estimating the frequency of monocytes, and T cells and MDSCs subtypes according to toxicity development. These analyses were performed with R packages v. 4.3.1. Results: Overall, 20 patients with eTNBC undergoing NACT were enrolled from July 2022 to February 2024. 12 patients developed irAEs (60%); severe adverse events (grade 3 or higher) were observed in four patients (20%). Particularly, 7 patients experienced hypotiroidism (35%), 3 patients developed a cardiac event (15%), 1 patient had adrenal insufficiency (5%), 2 patients developed acute kidney injury (10%). irAEs led to discontinuation of pembrolizumab in 10 patients (50%). Considering the various types of peripheral white blood cells, patients with irAE had significantly higher level of monocytes compared to other ones (p = 0.004). Although, the analysis suggested a statistical trend in an augmented expression of non-classical monocytes (CD14-, CD16+), the small sample size precluded statistical significance (p = 0.08). Patients experiencing irAEs showed also an increased expression of T-senescent lymphocytes (p= 0.08). Then, considering patients with irAEs who required treatment discontinuation we observed higher levels of monocytes (p=0.03), especially for the non-classical type (p=0.02). Conclusion: the addition of immunotherapy to NACT is known to significantly increase the pCR rate and improve the survival outcomes. Despite that, the KEYNOTE-522 regimen is marked by a high rate of adverse events and predictive biomarkers useful to their identification are needed. Our study suggest that peripheral white blood count can be an accessible and easy way to early detect patients with higher risk to develop irAEs, but further studies with larger samples are needed to confirm our findings. Citation Format: Benedetta Conte, Beatrice Ruffilli, Ida Taglialatela, Veronica Martini, Simone Gobbato, Valentina Rossi, Francesca D’Avanzo, Francesca Vezzoli, Giorgia Ferrari, Carmen Branni, Jacopo Gennari, Alessandra Gennari. Peripheral blood cells as predictors of immune-related toxicity in early triple negative breast cancer (eTNBC) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P1-04-10.