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

Abstract

This study (ORIENT-4) aimed to assess the efficacy and safety of sintilimab, a humanized anti-PD-1 antibody, in patients with relapsed/refractory extranodal NK/T cell lymphoma (r/r ENKTL). ORIENT-4 is a multicenter, single-arm, phase 2 clinical trial (NCT03228836). 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 criteria. Twenty-eight patients with r/r ENKTL were enrolled from August 31, 2017 to February 7, 2018. Twenty-one patients (75.0%, 95% CI: 55.1-89.3%) achieved an objective response. With a median follow-up of 30.4 months, the median overall survival (OS) was not reached. The 24-month OS rate was 78.6% (95% CI, 58.4-89.8%). Most treatment-related adverse events (TRAEs) were grade 1-2 (71.4%), and the most common TRAE was decreased lymphocyte count (42.9%). Serious adverse events (SAEs) occurred in 7 (25.0%) patients, and no patient died of adverse events. Sintilimab is effective and well tolerated in patients with r/r ENKTL and could be a novel therapeutic approach for the control of ENKTL in patients.

Conflict of interest statement

The authors declare no competing interests.

© 2021. The Author(s).

Figures

Fig. 1

Response to sintilimab in patients with relapsed/refractory NK/T cell lymphoma. a Analysis of time to response and duration of response. Patient 02004 was evaluated as stable disease after experiencing pseudo-progression. b Subgroup analysis of ORR

Fig. 2

Overall survival with sintilimab in patients with NK/T cell lymphoma. a Overall survival in all patients (28 patients) (X-axis refers to time of follow-up in months). b Overall survival in patients with pseudo-progression (5 patients) (X-axis refers to time of follow-up in months). c Overall survival in patients with the response pattern displayed as transient flares in different nodal groups without overall progression in the original target lesions (14 patients) (X-axis refers to time of follow-up in months)

Fig. 3

Patterns of radiologic tumor pseudo-progression after sintilimab. This picture shows CT imaging of a 59-year-old female patient in stage IV involving the head and neck area, mediastinum, and shank (left). This patient was first diagnosed with ENKTL in 2017 and previously received three cycles of L-asparaginase plus gemcitabine and oxaliplatin (GELOX) followed by local radiotherapy (50 Gy). On January 31, 2018, after progressive disease, the patient participated in ORIENT-4 and received sintilimab 200 mg Q3W. Six weeks after treatment, most lesions regressed, while a new lesion appeared on the right mediastinal pleura (middle), which had not been observed before. Twenty-four weeks after treatment, CT imaging showed further regression of right mediastinal pleura lesions, with the appearance of new lesions in week 6; the patients achieve a complete response (right). The areas marked by red cycles were new lesions