Anti-metabolic agent pegaspargase plus PD-1 antibody sintilimab for first-line treatment in advanced natural killer T cell lymphoma

扫码查看

原文链接

NETL
NSTL
万方数据

外文摘要：Natural killer T cell lymphoma(NKTCL)is highly aggressive,with advanced stage patients poorly responding to intensive chemotherapy.To explore effective and safe treatment for newly diagnosed advanced stage NKTCL,we conducted a phase Ⅱ study of anti-metabolic agent pegaspargase plus PD-1 antibody sintilimab(NCT04096690).Twenty-two patients with a median age of 51 years(range,24-74)were enrolled and treated with induction treatment of pegaspargase 2500 IU/m2 intramuscularly on day 1 and sintilimab 200 mg intravenously on day 2 for 6 cycles of 21 days,followed by maintenance treatment of sintilimab 200 mg for 28 cycles of 21 days.The complete response and overall response rate after induction treatment were 59％(95％CI,43-79％)and 68％(95％CI,47-84％),respectively.With a median follow-up of 30 months,the 2 year progression-free and overall survival rates were 68％(95％CI,45-83％)and 86％(95％CI,63-95％),respectively.The most frequently grade 3/4 adverse events were neutropenia(32％,n=7)and hypofibrinogenemia(18％,n=4),which were manageable and led to no discontinuation of treatment.Tumor proportion score of PD-L1,peripheral blood high-density lipoprotein cholesterol,and apolipoprotein A-I correlated with good response,while PD-1 on tumor infiltrating lymphocytes and peripheral Treg cells with poor response to pegaspargase plus sintilimab treatment.In conclusion,the chemo-free regimen pegaspargase plus sintilimab was effective and safe in newly diagnosed,advanced stage NKTCL.Dysregulated lipid profile and immunosuppressive signature contributed to treatment resistance,providing an alternative therapeutic approach dual targeting fatty acid metabolism and CTLA-4 in NKTCL.

作者：

Jie Xiong、Shu Cheng、Xiao Gao、Shan-He Yu、Yu-Ting Dai、Xin-Yun Huang、Hui-Juan Zhong、Chao-Fu Wang、Hong-Mei Yi、Hao Zhang、Wei-Guo Cao、Rong Li、Wei Tang、Yan Zhao、Peng-Peng Xu、Li Wang、Wei-Li Zhao

展开 >

作者单位：

Shanghai Institute of Hematology,State Key Laboratory of Medical Genomics,National Research Center for Translational Medicine at Shanghai,Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai,China

Department of Nuclear Medicine,Shanghai Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,China

Department of Pathology,Shanghai Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,China

Department of Otolaryngology,Shanghai Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,China

Department of Radiation,Shanghai Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,China

Department of Hematology,Navy Medical Center of PLA,Shanghai,China

Pôle de Recherches Sino-Français en Science du Vivant et Génomique,Laboratory of Molecular Pathology,Shanghai,China

展开 >

基金：

国家自然科学基金国家自然科学基金国家重点研发计划Chang Jiang Scholars Program,Shanghai Rising-Star ProgramShanghai Municipal Commission of Science and Technology ProjectShanghai Municipal Education Commission Gaofeng Clinical Medicine Grant SupportShanghai Municipal Education Commission Gaofeng Clinical Medicine Grant SupportShanghai Municipal Education Commission Gaofeng Clinical Medicine Grant SupportClinical Research Plan of Shanghai Hospital Development CenterMulticenter Clinical Research Project by Shanghai Jiao Tong University School of MedicineMulti-center Hematology-Oncology Protocols Evaluation System(M-HOPES)network from ChinaSamuel Waxman Cancer Research FoundationCenter for High Performance Computing at Shanghai Jiao Tong University

项目编号：

82130004822701942022YFC250260023QA140610023141903100201522062015220820161303SHDC2020CR1032BDLY201601

出版年：

2024

DOI：

10.1038/s41392-024-01782-8

信号转导与靶向治疗(英文)

CSTPCD

ISSN：

年,卷(期)：2024.9(4)

参考文献量51