P1240: 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

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, which has been shown to be effective in treatment of r/r-lymphoma with an acceptable safety. Etoposide is an important chemotherapeutic agent in the treatment of ENKTL. Here we present preliminary results of anti-PD-1 antibody combined with chidamide, lenalidomide and etoposide for the treatment of r/r-lymphoma. Aims: To explore the efficacy and safety of 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). 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 biw), Lenalidomide (25mg d1-10) and Etoposide (100mg/m2 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 March 2022, 23 patients were screened and 20 eligible patients were enrolled from 4 centers in China, with median age at 36.5 years (range 17-60), 16 (80.0%) male, 15 (75.0%) patients with stage Ⅲ-Ⅳ of disease at screening, 10 (50.0%) patients received ≧2 lines of prior systemic therapy. Of 19 response evaluable patients, 18 (94.7%) achieved response including 9 (50%) patients with CR. The median time to initial response was 6.0 weeks (6-12 weeks). The 12-month PFS rate was 86.8%. 19 patients reported treatment-related AEs (TRAEs). The most frequently observed TRAEs were anemia (15 patients,78.9%), neutropenia (14 patients, 73.6%), leukopenia(11 patients, 57.9%), nausea (10 patients, 52.6%), thrombocytopenia (9 patients, 50%). The most frequent Grade (G) ≥3 TRAEs were neutropenia (9 patients, 50%). Immune-related AEs were reported in 4 patients (21.1%) with G1 hypothyroidism. No death was related to the study. Image:Summary/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, although further investigation is warranted.