302MO - Development of a flow cytometry-based whole-blood prognostic immune signature in metastatic cancer patients treated with immune checkpoint inhibitors

Background

The predictive power of programmed cell death ligand 1 (PD-L1) for treatment response to PD-1/PD-L1 immune checkpoint inhibitors (ICI) is not satisfactory. Recent biomarker research focuses on early immunological changes in the peripheral blood to predict treatment response to ICI. Within this prospective ST-ICI trial, pre-planned biomarker analysis was performed and we developed a flow cytometry-based whole-blood prognostic immune signature (FCBPS) to predict overall survival (OS) benefit of cancer patients treated with ICI.

Methods

The predictive power of programmed cell death ligand 1 (PD-L1) for treatment response to PD-1/PD-L1 immune checkpoint inhibitors (ICI) is not satisfactory. Recent biomarker research focuses on early immunological changes in the peripheral blood to predict treatment response to ICI. Within this prospective ST-ICI trial, pre-planned biomarker analysis was performed and we developed a flow cytometry-based whole-blood prognostic immune signature (FCBPS) to predict overall survival (OS) benefit of cancer patients treated with ICI.

Results

A total of 104 patients were prospectively enrolled. Eighty-nine patients provided blood samples. The identified FCBPS signature bases on five immune cell subtypes: neutrophils, plasmacytoid dendritic cells (pDCs), natural killer (NK)T cells (CD56⁺/CD16⁺), monocytes (CD14^high) and CD8⁺ T cells (PD-1⁺). This signature achieved a high accuracy (C-index 0.74 vs 0.71) for predicting OS benefit in the training and validation cohort. Both in the training and validation cohort, the low-risk group had significantly longer OS than the high-risk group (HR 0.26, 95% CI: 0.12-0.56, p=0.00025; HR 0.30, 95% CI: 0.10 -0.91, p=0.024, respectively). In the whole cohort, FCBPS is a predictor of OS (HR_OS=0.28, 95% CI: 0.15-0.52) and progression-free survival (HR_PFS=0.22, 95% CI: 0.12-0.39) that remained independent in multivariate analyses and subgroup analyses after adjusting for clinical and pathological factors.

Conclusions

The flow cytometry-based whole-blood prognostic signature (FCBPS) is a powerful predictor for metastatic cancer patients who benefit from ICI treatment.

Clinical trial identification

NCT03453892; on January 24, 2018.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.