Newly diagnosed extranodal natural killer/T cell lymphoma (ENKTL) treated by anti‐PD‐1 antibody plus histone deacetylase inhibitor followed by P‐GemOx regimen

Abstract

Background: ENKTL is a highly aggressive NHL with a higher incidence in Asia. In 2020 ASH meeting, we reported Sintilimab(anti-PD-1 antibody) plus Chidamide(an oral subtype-selective HDACi) yielded effective antitumor activity, durable response with mild toxicity in patients with relapsed or refractory ENKTL. We then initiated this exploratory study to investigate the efficacy and safety of Sintilimab plus Chidamide(SC) for patients with newly diagnosed ENKTL. Methods: This trial enrolled eligible patients with newly diagnosed ENKTL(ND-ENKTL); ECOG score ≤2; at least one measurable or evaluable lesion. All patients received 2–3 cycles of Sintilimab (200 mg) plus Chidamide (30 mg, twice a week). For patients with early stage, 2 cycles of SC were given, subsequent 2–4 cycles of P-GemOx regimen administered and followed by involved field radiotherapy (IFRT). For advanced stage, patients were treated with 3 cycles of SC and 3–6 cycles of P-GemOx. The primary study endpoints are the ORR of SC and end of treatment assessed according to the lymphoma response to immunomodulatory therapy criteria (LYRIC). Key secondary endpoints included DOR, PFS, OS and safety. Results: From July 2019 to Nov 2021, 42 eligible patients were enrolled from Sun Yat-sen University Cancer Center. The median age was 47.5 (range, 20–81) years, 16(38%) patients with stage III-IV, 15(31%) patients with PINK-E score≥3. All patients were evaluated for efficacy. For stage I-II, 21(81%) patients achieved response, including 18(69%) CR patients with SC. After 2 cycles of SC, 17(94%) of 18 CR patients chosen to continue SC treatment. Only 1 (6%) PR patients accepted 2 cycles of P-GemOx and got CR after chemotherapy. Twenty-five (96%) patients obtained CR after IFRT. For stage III–IV, 9(56%) patients achieved response with 13%(2/16) CR, 3(33.3%) patients experienced rapid progression disease (RPD) in SC portion. Ten (63%) patients entered P-GemOx portion including 1 RPD patient. Thirteen (81%) patient got ORR with 69% (11/16) CR after whole treatment. The median follow-up time was 24.1(5.4–44.3) months. The 2-year PFS and OS rate were 76% and 78%, the prognosis of early stage is better than advanced stage (Fig. 1). Two RPD patients died within one month. Circulating EBV-DNA clearance after SC significantly correlated with superior outcome. Forty(95.2%) patients reported treatment-related adverse effects (TRAEs). The most common TRAEs (≥10%) were neutropenia (43%), thrombocytopenia (38%), elevated transaminase (29%), and anemia (24%). The most common grade 3 TRAEs (≥10%) was elevated transaminase (10%), no grade 4 TRAEs. Keywords: aggressive T-cell non-Hodgkin lymphoma, extranodal non-Hodgkin lymphoma, immunotherapy No conflicts of interests pertinent to the abstract.