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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care

1530 - Peripheral Blood Mononuclear Cell Biomarkers Predict Response to Immune Checkpoint Inhibitor Therapy in Metastatic Breast Cancer

Date

22 Oct 2018

Session

Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care

Presenters

Yuan Yuan

Citation

Annals of Oncology (2018) 29 (suppl_8): viii90-viii121. 10.1093/annonc/mdy272

Authors

Y. Yuan1, W. Hou2, S. Padam1, P. Frankel3, M.S. Sedrak1, J. Portnow1, J. Mortimer1, C. Yeon1, A. Hurria1, A. Tang1, N. Martinez1, P. Lee2

Author affiliations

  • 1 Medical Oncology, City of Hope, 91010 - Duarte/US
  • 2 Immunology, City of Hope, 91010 - Duarte/US
  • 3 Biostatistics, City of Hope, 91010 - Duarte/US
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Resources

Abstract 1530

Background

The role of immune checkpoint PD-1/PD-L1 inhibitor (ICI) in breast cancer (BC) is being investigated in clinical trials. Preclinical evidence strongly supports the synergistic effects of CDK4/6 inhibitor and ICI. A phase II trial is testing the safety and efficacy of the combination of letrozole, palbociclib and pembrolizumab in patients with hormone receptor positive (HR+) BC (NCT02778685). Currently, there is no well-defined circulating biomarker to predict response to ICI.

Methods

Peripheral blood mononuclear cells (PBMC) were collected at day 1 of cycles 1 (pre-treatment), 2, 4, 6 and 8. The comprehensive characterization of 14 innate cell types, 7 adaptive T-cells, and 16 exhaustion-related T-cells was performed using 15-color flow cytometry. Core biopsies were taken at baseline and optionally on-study to assess immune cell subsets.

Results

Preliminary analysis included nine patients with the following responses by RECIST 1.1: 1 complete response, 4 partial responses, 2 stable disease, and 2 progression of disease. Analysis showed correlation of clinical response to high baseline levels of γδ T-cells (r = 0.74, p = 0.02) and exhausted T-cells: CD4+PD-1+KLRG1+ (r = 0.74, p = 0.02), CD4+PD-1+CD160+ (r = 0.71, p = 0.02), and CD4+PD-1+TIM3+ (r = 0.71, p = 0.03). Most patients showed a decrease in the number of CD33hi myeloid-derived suppressor cells (p = 0.04) and CD4+PD-1+TIGIT+ exhausted T-cells (p = 0.04) in peripheral blood at C2D1. Strong indicators of clinical response included increased CD33low myeloid-derived suppressor cells (r = 0.70, p = 0.04) and decreased type-1 CD8+ T-cells (r = 0.81, p = 0.009) at C4D1.

Conclusions

High pre-treatment peripheral blood exhausted CD4+ T-cells is associated with clinical response to ICI in HR+BC. Further analysis including tumor tissue immune profiling is currently ongoing to verify these findings.

Clinical trial identification

NCT02778685.

Legal entity responsible for the study

City of Hope.

Funding

City of Hope, Merck, Pfizer.

Editorial Acknowledgement

Disclosure

Y. Yuan: Industry funded research: Pfizer, Merck, Puma, GTX, Novartis, Eisai; Advisory board: Puma, Novartis, Eisai; Speaker Bureau: Eisai. All other authors have declared no conflicts of interest.

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