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