Abstract P1-04-12: Systemic immune response to a Phase I/II trial of Durvalumab concomitant with neoadjuvant chemotherapy in early stage TNBC

Abstract

Abstract Background Peripheral blood cells and secreted products are important regulators of the systemic immune response. Circulating cytokines have been shown to predict severity of immune-related toxicity in melanoma patients that received combination anti-PD-1-based immunotherapy. In this study, we evaluated 38 serum cytokines and the peripheral blood t cell receptor (TCR) immune repertoire of 66 patients with TNBC for associations with pCR, treatment phase (PRE; POST), and immune related treatment emergent adverse events (TEAEs). Methods Serum and peripheral blood buffy coats were collected at pre-treatment (week 0) and at post-treatment (~ week 24). MILLIPLEX MAP Human Cytokine/Chemokine Magnetic Bead Panel was run in duplicate and read on the Luminex platform. Genomic DNA was isolated using QIAGEN Kits per manufacturer’s instructions. TCR immune repertoire profiling was performed using the Immunoseq at Adaptive Biotechnologies. Statistical analysis was performed in R. P-values < 0.05 for serum cytokines and P-values < 0.05 for TCR were considered significant. Results Pielou’s diversity index showed no difference between patient groups for TCR (P>0.319). Baseline samples had increased sCD40L, EGF, and IL-10 in patients with RD compared to pCR (P< 0.05). Baseline samples had decreased FGF2 and IFN gamma in patients with immune related TEAEs compared to those with no immune related TEAEs (P< 0.05). Comparison of Pre- vs Post-treatment revealed that EGF, MIP1 alpha, IL-1 alpha, IL-8, and MDC were increased in patients with pCR compared to those with RD. Comparison of Pre- vs. Post- also revealed increased levels of cytokines (EGF, IL-7, IFN gamma, GM-CSF) in samples in patients with immune related TEAEs (P< 0.05) compared to those patients without immune-related TEAEs. It also revealed that there was an increase in a subset of cytokines (IL-7, IL-4, MCP3, and IL-1 alpha) in patients that presented with serious immune related TEAEs (P< 0.05) compared to those patients without serious immune-related TEAEs. Conclusions There are subsets of circulating inflammatory cytokines that may be associated with treatment emergent adverse events in patients with TNBC treated with Durvalumab concomitant with standard of care chemotherapy. Citation Format: Kim Blenman, Michal Marczyk, Julia Foldi, Vignesh Gunasekharan, Andrea L.M. Silber, Lajos Pusztai. Systemic immune response to a Phase I/II trial of Durvalumab concomitant with neoadjuvant chemotherapy in early stage TNBC [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-04-12.