Sintilimab for relapsed/refractory (r/r) extranodal NK/T cell lymphoma (ENKTL): Extended follow-up on the multicenter, single-arm phase II trail (ORIENT-4).

Abstract

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Background: Patients with r/r ENKTL have a poor prognosis after failing an asparaginase-based regimen. The overexpression of PD-L1 induced by EBV infection is a potential mechanism for ENKTL to avert immune surveillance. Sintilimab, a fully human anti-PD-1 monoclonal antibody, has demonstrated efficacy in r/r ENKTL after the primary analysis of the ORIENT-4 study. Here, we report the updated efficacy and safety results with extended follow-up. 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 per Lugano 2014. Data cut-off date for this analysis was Jan 17, 2020. Results: A total of 28 patient were enrolled and treated. With a median follow-up of 26.9 months (range, 23.3 to 28.6), the median treatment duration was 24.15 months (range, 1.4 to 28.7). Of 20 patients with progressive disease (PD) by investigator per Lugano 2014 criteria, 19/20 (95%) patients received treatment beyond PD. The median OS has not been reached and 24-month OS rate was 78.6% (95% CI, 58.4% to 89.8%). ORR was 67.9% (95% CI, 47.6% to 84.1%), 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. Median duration of response was 4.1 months (range, 1.9 to 15.2+). After treatment, the mean EQ-5D-5L VAS Score (from 79.3 to 90.8), EQ-5D-5L Index Value (from 0.8 to 0.9) and EORTC QLQ-C30 (from 70.5 to 87.3) were all increased. The Treatment-related adverse events (TRAEs) of any grade occurred in 28 (100%) pts; grade 3 occurred in 11 (39.4%) pts, most commonly, decreased lymphocyte count (2 [7.1%]) and diabetes (2 [7.1%]); no grade 4-5 TRAE. Conclusions: In addition to an encourage response, sintilimab also demonstrated long-term clinical benefit, with 78.6% of 24-month OS rate, and favorable long-term safety profile after extended follow-up. Considering the high rate (95%) of treatment beyond PD, Lugano 2014 may not be a suitable criteria for evaluating the efficacy of anti-PD-1 antibody in r/r ENKTL. Clinical trial information: NCT03228836 .