Anti-PD-1-Antibody (Tislelizumab) Combined with Deacetylase Inhibitor (Chidamide), Lenalidomide and Etoposide for the Treatment of Refractory/Relapsed Extranodal Natural Killer/T Cell Lymphoma, Nasal Type (r/r-ENKTL): Preliminary Results from a Prospective, Multicenter, Single -Arm, Phase II Trial

Abstract

Background: Extranodal Natural Killer/T Cell Lymphoma(ENKTL) is a highly aggressive non-Hodgkin lymphoma (NHL), with higher incidence in Asia, which is related to Epstein-Barr virus (EBV) infection. Patients with r/r-ENKTL have a poor prognosis, and is lack of effective treatment. Anti-PD-1-Antibody plus Chidamide was effective and well tolerated on r/r-ENKTL (SCENT Trial, 2020 ASH). Lenalidomide is an immunomodulatory agent, previous studies showed activity in r/r-lymphoma with an acceptable safety. Etoposide is an important chemical agent in the treatment of ENKTL. Here we present preliminary results of Anti-PD-1 antibody combined with Chidamide, Lenalidomide and Etoposide for the r/r-ENKTL.Methods: This was a prospective, single-arm, open-label, multi-center, phase II clinical trial. This trial enrolled eligible patients with histologically confirmed r/r-ENKTL failing from at least 1-line treatment; ECOG performance status ≤ 2; adequate organ function and bone marrow function; and at least one measurable or evaluable lesion. Patients received 6 cycles of Tislelizumab (200mg), Chidamide (20mg q3d), Lenalidomide (25mg d1-10) and Etoposide (100mg/m 2 d1-3), every 21 days cycle. Then received 10 cycles of Tislelizumab (200mg) maintenance treatment, every 21 days cycle. The primary endpoints were objective response rate (ORR) based on Lugano 2014 criteria, duration of response (DOR), progression-free survival (PFS), overall survival (OS) and disease control rate (DCR). Secondary endpoints were median survival time (MST) and safety. Adverse events (AE) were rated according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) 5.0. This trial is registered at ClinicalTrials.gov (NCT04038411).Results: From July 2020 to July 2021, 12 patients were screened and 10 eligible patients were enrolled, median age was 36.5 years (range 18-58), 8 (90.0%) male, 8(80.0%) patients with stage Ⅲ-Ⅳ of disease at screening, 4 (40.0%) patients received ≥2 lines of prior systemic therapy. Of 8 response evaluable patients, 7 (87.5%) achieved response including 5 (62.5%) patients with CR. The median time to initial response was 4.0 weeks (2-6 weeks). 10 Patients reported treatment-related AEs (TRAEs). The most frequently observed TRAEs were neutropenia (10 patients), thrombocytopenia (4 patients), transaminase increased (3 patients), nausea (4 patients). The most frequent Grade (G) ≥3 TRAEs were neutropenia (6 patients). Immune-related AEs were reported in 2 patients with G1 hypothyroidism. No death was related to the study.Conclusion: Tislelizumab combined with Chidamide, Lenalidomide and Etoposide regimen have a very high response rate in r/r-ENKTL for the first time, and the safety is under control. It is a promising therapeutic option for this population, further investigation is warranted. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.