Abstract
The impact of serum levels of soluble programmed cell death ligand 1 (sPD-L1) on prognosis in patients with Epstein-Barr virus-associated malignancies has never been investigated. We prospectively measured pre- and post-treatment serum sPD-L1 levels and evaluated their prognostic value in 97 patients with newly diagnosed, early stage extranodal NK/T-cell lymphoma (ENKTCL) treated with asparaginase-based chemotherapy followed by radiotherapy. For predicting survival outcomes, serum sPD-L1 levels of 3.23 ng/mL and 1.12 ng/mL were respectively identified for pre- and post-treatment cut-off levels. Patients with high pretreatment (>3.23 ng/mL) had shorter progression-free survival (PFS) and overall survival (OS). In a multivariate survival analysis, post-treatment sPD-L1 >1.12 ng/mL, treatment response (complete vs. non-complete response), and stage II disease were independent prognostic factors for shorter PFS and OS. In patients with a complete response, post-treatment sPD-L1 >1.12 ng/mL was associated with shorter PFS and OS. In patients with high pretreatment sPD-L1 levels (>3.23 ng/mL), low post-treatment sPD-L1 level (≤1.12 ng/mL) correlated with longer PFS and OS. Our data suggest the post-treatment sPD-L1 level is a potent biomarker for predicting early relapse and poor prognosis in early stage ENKTCL patients treated with asparaginase, and may be a useful marker of minimal residual disease.
Highlights
Extranodal NK/T-cell lymphoma (ENKTCL) is an aggressive non-Hodgkin’s lymphoma [1] and is closely associated with Epstein-Barr virus (EBV) infection [2]
In this study of ENKTCL patients receiving an asparaginase-based chemotherapy regimen, we found that high pre-treatment soluble programmed cell death ligand 1 (sPD-L1) levels were associated with poor treatment response and post-treatment sPD-L1 level was an independent prognostic factor for both progression-free survival (PFS) and overall survival (OS)
Post-treatment sPD-L1 levels identified patients with a complete response (CR) after treatment who had a high risk of relapse and poor prognosis
Summary
Extranodal NK/T-cell lymphoma (ENKTCL) is an aggressive non-Hodgkin’s lymphoma [1] and is closely associated with Epstein-Barr virus (EBV) infection [2]. Because of the high rate of locoregional and systemic recurrence with standard radiotherapy treatment alone, chemotherapy has been integrated into the management of ENKTCL [4]. There is increasing evidence that asparaginase-based chemo-radiotherapy regimens are superior to anthracyclinebased regimens in the treatment of ENKTCL due to overexpression of the multidrug-resistant (MDR) gene in tumor cells [5, 6]. Asparaginase-based chemotherapy combined with radiotherapy, which significantly improves long term survival rates, has become the standard treatment for ENKTCL. Nearly 30% of patients with localized ENKTCL still develop local and systemic failures and die due to disease progression [6, 7]. Identification of patients with a high risk of relapse is crucial in ENKTCL treatment
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