Abstract
Background:Currently, available treatments cannot achieve satisfactory efficacy in patients with relapsed/refractory (r/r) extranodal natural killer/T-cell lymphoma (ENKTL). Programmed death-1 (PD-1) inhibitors achieve clinical benefits for patients with solid or hematologic malignancies. This study (ORIENT-4) aimed to define the efficacy and safety of sintilimab in patients with r/r ENKTL. Methods: ORIENT-4 is a multicenter, single-arm, phase 2 clinical trial. Patients with r/r ENKTL who failed to at least one asparaginase-based regimen were enrolled to receive sintilimab 200 mg intravenously every 3 weeks for up to 24 months. The primary endpoint was the objective response rate (ORR) based on Lugano 2014. Findings: From August 31, 2017 to February 7, 2018, 28 r/r ENKTL patients were enrolled. Of them, 19 (67∙9%, 95% confidence interval: 47∙6%-84∙1%) achieved an objective response. With a median follow-up of 20∙3 months, the median overall survival (OS) was not reached. The 1-year OS rate was 82∙1%. Most treatment-related adverse events (TRAEs) were grade 1-2 (60∙7%). The most common TRAE was decreased lymphocyte count (46∙4%). Serious adverse events occurred in seven (25∙0%) patients, and none were related to sintilimab. No patient died of adverse events. Interpretation: Sintilimab is effective and well-tolerated in patients with r/r ENKTL, suggesting that sintilimab could be a novel therapeutic approach for the control of ENKTL in patients who failed to one line of therapy based on asparaginase. Trial Registration: (ClinicalTrials.gov, #NCT03228836) Funding Statement:This trial was sponsored by Innovent Biologics, Inc., and partly supported by the National Natural Science Foundation of China (81720108002), the National Science and Technology Major Project (2018ZX09734-007) and Excellent Youth Foundation Project of Jiangsu Province (Grant No.BK20160099). The study drug was provided by Innovent Biologics, Inc. Declaration of Interests: LXYX, HZ, and XS are employed by Innovent Biologics, Inc. The remaining authors have no financial relationships. Ethics Approval Statement: This study was approved by the ethics committee of each participating center and conducted in accordance with the principles of the Declaration of Helsinki and the Good Clinical Practice guideline. All patients provided written informed consent prior to any study procedure.
Highlights
Extranodal natural killer (NK)/T cell lymphoma (ENKTL) is a highly aggressive subtype of non-Hodgkin lymphoma (NHL) with a high incidence in Asia and Latin America.[1]
Patients were excluded because the lesion was
For QLQ-C30, the mean score increased from 70.5 at baseline to 85.4 at week 24 (P < 0.0001) and remained between 82.0 and 87.3 from weeks 24 to 96 (Supplementary Fig. S3C). This phase 2 study showed that sintilimab was effective and well tolerated in patients with r/r ENKTL
Summary
Extranodal natural killer (NK)/T cell lymphoma (ENKTL) is a highly aggressive subtype of non-Hodgkin lymphoma (NHL) with a high incidence in Asia and Latin America.[1] In China, ENKTL accounts for 6.6% of all NHL and 28.1% of peripheral T lymphomas (PTCLs).[2] The 5-year overall survival (OS) of patients with ENKTL is 40–50%.1. ENKTL shows a poor response to conventional anthracyclinebased chemotherapy due to the high expression of the multidrug resistance P-glycoprotein. Asparaginase-based regimens are effective for ENKTL with an objective response rate (ORR) of 67–79% and a complete response (CR) rate of 45–61%.3–5. Patients who failed asparaginase-based therapy have limited treatment options with a median survival of
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