141P - Circulating immune cells predict immunotherapy benefit in patients with triple negative breast cancer: Preliminary results from the IRIS study

Background

Immune checkpoint inhibitors (ICIs) have improved the outcomes of patients with both early (eTNBC) and metastatic triple negative breast cancer (mTNBC). Yet, mechanisms of response and resistance to ICIs remain unknown, leading to suboptimal patients selection. In this prospective study we assessed whether circulating immune cells are determinants of ICIs efficacy in TNBC.

Methods

IRIS is an ongoing multicenter trial assessing blood immune biomarkers in patients with eTNBC and mTNBC treated with ICI-based therapy. Blood is collected before ICIs initiation and at end of treatment/progression (EoT/PD). Flow cytometry is used to profile monocytes, dendritic cells (DCs), and T CD4, T CD8, B, natural killer (NK) lymphocytes. FACSDiva, FloJo and R softwares were used for this preliminary analysis.

Results

From 09/2020 to 04/2024, 44 patients were enrolled, 32 (73%) with eTNBC and 12 (27%) with mTNBC. Median follow up was 19 months (IQR 7.2-NR). Primary memory B (Mann-Whitney p=0.003), class switched B (p=0.012), and effector memory (EM) CD4 (p=0.034) were higher in eTNBC, while patients with mTNBC had higher regulatory/unprimed cells, i.e. transitional B (p=0.049), naïve B (p=0.019), plasmacells (p=0.007), and CD11c+ CD123+ dentritic cells (p=0.015). In eTNBC, B cells were associated with pCR following ICIs (OR 1.26, 95% CIs 1.00-1.78, p=0.050). Overall, Treg, Treg memory, and Th17 CD4 were predictors of improved progression free survival (PFS) and overall survival (OS), while immature plasmacells predicted worse PFS and OS (Table). An increase in myeloid DCs (mDC) and a decrease in terminally differentiated EM CD8 (TEMRA) and NK cells was observed at PD in patients with paired samples (n=5, Wilcoxon p=0.063, 0.062, 0.060) Table: 141P

Conclusions

Circulating immune cells predict TNBC outcomes following ICIs. TEMRA, NK and mDC changes thorough PD suggests their potential implication in ICI resistance. More results will be presented at the Congress.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

AIRC - Associazione Italiana per la Ricerca contro il Cancro.

Disclosure

B. Conte: Other, Personal, Other, travel expenses: Pfizer; Financial Interests, Personal, Invited Speaker: Veracyte. A. Gennari: Financial Interests, Personal, Invited Speaker: Eisai, Lilly, Gilead; Financial Interests, Personal, Advisory Board: Eisai, Novartis, AstraZeneca, Roche, Gentili, Daiichi Sankyo, Pfizer, Lilly, Menarini Stemline; Financial Interests, Personal, Invited Speaker, Invited speaker at public conferences: Exact Science; Non-Financial Interests, Principal Investigator: Italian Association for Cancer Research - IG Project, EraNET Transcan, PRIN 2022 - MIUR; Non-Financial Interests, Other, Pi of a project within the primary project: MIUR- Italian Ministry of University and Research - Department of Excellence; Non-Financial Interests, Institutional, Product Samples, Provision of dietary supplement samples for clinical research: Pharmanutra. All other authors have declared no conflicts of interest.