Extranodal natural killer/T cell lymphoma(ENKTCL) is a distinct lymphoid neoplasm with
aggressive course and poor outcomes. Optimal treatment strategies for advanced ENKTCL have
not been fully defined.Patients with disseminated or relapsed disease have a very poor
outcome,and there is no standard management for relapsed or refractory disease.Combination
chemotherapy remains the mainstay of treatment.In small retrospective studies have observed
very good response and survival rates in patients treated with L-asparaginase.In several
prospective study that examined relapsed/refractory patients treated with SMILE outside a
trial setting,the efficacy sounds good. But treatment related mortality was 7%. The regimen
has toxicity, with careful attention to adverse effects and skill acquired through
experience. Chidamide, a oral subtype-selective histone deacetylase inhibitor monotherapy was
effective on the patients with relapsed or refractory ENKTCL in our study. Objective response
rate was 50.0% (6/12) with complete response(CR) rate 33.3 %( 4/12).All four CR patients were
still in disease-free more than 6.9 months (6.9-10.5). ENKTCL are invariably infected by
Epstein-Barr virus(EBV).EBV-infected lymphoma cells upregulate programmed death ligand 1
(PDL1), ligand of the inhibitory receptor programmed death 1(PD1) on T cells.Ligation of PDL1
on lymphoma cells with PD1 on effector T cells suppresses T-cell cytotoxicity. The PDL1/PD1
axis is therefore a potential mechanism for ENKTCL to avert effector T-cell targeting.PD1
blockadewith pembrolizumab was a potent strategy for ENKTCL failing L-asparaginase regimens
in several reports.We carried out a single, open-label, multicenter clinical trial enrolled
patients with relapsed or refractory ENKTCL to safety and efficacy of sintilimab in
combination With chidamide.
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