Cancer Res Treat.  2019 Apr;51(2):832-840. 10.4143/crt.2018.311.

Dynamics of Soluble Programmed Death-Ligand 1 (sPDL1) during Chemotherapy and Its Prognostic Implications in Cancer Patients: Biomarker Development in Immuno-oncology

• Ha H
• Bang JH
• Nam AR
• Park JE
• Jin MH
• Bang YJ
• Oh DY

• KMID: 2464428
• DOI: http://doi.org/10.4143/crt.2018.311

Abstract

PURPOSE
The soluble programmed death-ligand 1 (sPDL1) has immunosuppressive activity and is a candidate biomarker for immuno-oncology drug development. In this study, we measured sPDL1 at pre- and post-chemotherapy and at disease progression to uncover the dynamics of sPDL1 during treatment in biliary tract cancer (BTC) patients.
MATERIALS AND METHODS
From 90 BTC patients (training cohort, 53; validation cohort, 37) who were candidates for palliative first-line chemotherapy, blood was collected at pre- and post-chemotherapy (at the time of best response) and at disease progression. The sPDL1 levels were measured using an enzyme-linked immunosorbent assay. Responses to chemotherapy, overall survival (OS), and other prognostic factors including the neutrophil-lymphocyte ratio (NLR) were analyzed.
RESULTS
The OS of all patients was 11.5 months (confidence interval [CI], 9.7 to 16.2). The best response was complete response in seven (7.8%), partial response in 20 (22.2%), stable disease in 52 (57.8%), and disease progression (PD) in 11 patients (12.2%). Patients with high pre-chemotherapy sPDL1 (≥ 1.30 ng/mL) showed worse OS than patients with low prechemotherapy sPDL1 (9.1 months vs. 12.5 months, p=0.003). In multivariate analyses, high pre-chemotherapy sPDL1 (hazard ratio [HR], 1.96; 95% CI, 1.2 to 3.9; p=0.011) and high pre-chemotherapy NLR (HR, 1.82; 95% CI, 1.1 to 3.0; p=0.020) were independent poor prognostic factors for OS. At the time of PD, sPDL1 was increased significantly compared with pre-chemotherapy sPDL1 (1.59 ng/mL vs. 0.72 ng/mL, p=0.003).
CONCLUSION
The sPDL1 at pre-chemotherapy confers the prognostic value for OS in BTC patients under palliative chemotherapy. The dynamics of sPDL1 during chemotherapy correlate with disease burden and have prognostic value.

Keyword

Soluble PDL1; PDL1; Dynamics; Biomarkers; Prognosis

MeSH Terms

Biliary Tract Neoplasms
Biomarkers
Cohort Studies
Disease Progression
Drug Therapy*
Enzyme-Linked Immunosorbent Assay
Humans
Multivariate Analysis
Prognosis
Biomarkers

Figure

• 

  Fig. 1. Overall survival according to pre-chemotherapy soluble programmed death-ligand 1 (sPDL1). Baseline sPDL1 is correlated with overall survival in entire cohort (A), training cohort (B), and validation cohort (C). Cut-off value of sPDL1 is 1.30 ng/mL in three cohorts. High sPDL1 at pre-chemotherapy confers worse overall survival.

• 

  Fig. 2. Changes of soluble programmed death-ligand 1 (sPDL1) at disease progression. sPDL1 level at the time of disease progression is increased compared with pre-chemotherapy.

Reference

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