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.
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.
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 (CD14high) 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 (HROS=0.28, 95% CI: 0.15-0.52) and progression-free survival (HRPFS=0.22, 95% CI: 0.12-0.39) that remained independent in multivariate analyses and subgroup analyses after adjusting for clinical and pathological factors.
The flow cytometry-based whole-blood prognostic signature (FCBPS) is a powerful predictor for metastatic cancer patients who benefit from ICI treatment.
NCT03453892; on January 24, 2018.
The authors.
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All authors have declared no conflicts of interest.