Sintilimab for relapsed/refractory (r/r) extranodal NK/T-cell lymphoma (ENKTL): A multicenter, single-arm, phase 2 trial (ORIENT-4).

7504 Background: ENKTL account for more than 20% of the peripheral T-cell lymphoma in Asia. Patients with r/r ENKTL have a poor prognosis after failing an L-asparaginase based regimen, and the median overall survival is less than 6 months. The overexpression of PD-L1 induced by EBV infection is a potential mechanism for ENKTL to avert immune surveillance, and recent studies of PD-1 antibodies in pts with r/r ENKTL have demonstrated potential efficacy. Sintilimab, a fully human anti-PD-1 monoclonal antibody, has a safety profile consistent with other approved PD-1 antibodies and was approved for r/r classical Hodgkin lymphoma in China in 2018. This multicenter, single-arm, phase 2 study aims to validate the efficacy and safety of sintilimab monotherapy in patients with r/r ENKTL in China. Methods: Patients with pathologically confirmed r/r ENKTL were enrolled. Sintilimab was given 200 mg IV Q3W, until PD, death, unacceptable toxicity, or withdrawal from the study. Treatment beyond PD is allowed. Tumor response evaluation was performed by both PET-CT and CT/MRI with contrast. The primary endpoint was objective response rate based on LUGANO 2014 criteria. Data cut-off date for this analysis was Feb 2, 2019. Results: From Aug 31, 2017 to Feb 7, 2018, a total of 28 patients were enrolled: 60.7% male and the median age was 37 (range: 19–65) yr. Sixty-eight percent of patients were stage IV and 89.3% were ECOG PS ≥ 1. All patients had failed an L-asparaginase based regimen, the median lines of previous therapy were 3 (range: 1–13), 78.6% patients received prior radiotherapy and 7.1% had failed HSCT. Median duration of therapy was 14.04 (range: 1.4–17.3) months and 19 patients are still receiving sintilimab. Sixty-eight percent (19/28, 95%CI: 47.6%–84.1%) of patients achieved response (CR+PR), including 4 pts who experienced PD prior to having a response. DCR was 85.7%, including 5 pts who experienced PD before SD or response. The 1-year OS rate was 82.1% and the median OS has not been reached. Most TRAEs were G1–2 (67.9%) and no patients discontinued treatment due to AEs. The most common TRAE was decreased lymphocyte count (46.4%) and 84.6% were grade 1–2. SAEs occurred in 21.4% of patients and none were related to sintilimab. No patients died from AEs. Conclusions: Sintilimab is effective and well tolerated in r/r ENKTL and could be a promising treatment option for these patients. Early disease progression observed by PET scan in this study could be pseudoprogression as it did not correlate with poor outcome, which warrants further investigation. Clinical trial information: NCT03228836.