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

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 

机构地区：[1]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 [2]Department of Nuclear Medicine,Shanghai Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,China [3]Department of Pathology,Shanghai Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,China [4]Department of Otolaryngology,Shanghai Rujin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,China [5]Department of Radiation,Shanghai Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,China [6]Department of Hematology,Navy Medical Center of PLA,Shanghai,China [7]Pole de Recherches Sino-Francais en Science du Vivant et Genomique,Laboratory of Molecular Pathology,Shanghai,China

出　　处：《Signal Transduction and Targeted Therapy》2024年第4期1665-1674,共10页信号转导与靶向治疗（英文）

基　　金：supported,in part,by research funding from the National Natural Science Foundation of China (82130004 and 82270194);National key research and development program (2022YFC2502600);Chang Jiang Scholars Program,Shanghai Rising-Star Program (23QA1406100);Shanghai Municipal Commission of Science and Technology Project (23141903100);Shanghai Municipal Education Commission Gaofeng Clinical Medicine Grant Support (20152206,20152208,and 20161303);Clinical Research Plan of Shanghai Hospital Development Center (SHDC 2020CR1032B);Multicenter Clinical Research Project by Shanghai Jiao Tong University School of Medicine (DLY201601)。

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 ll 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%Cl,43-79%)and 68%(95%Cl,47-84%),respectively.With a median follow-up of 30 months,the 2 year progression-free and overall survival rates were 68%(95%Cl,45-83%)and 86%(95%Cl,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-l 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 profle and immunosuppressive signature contributed to treatment resistance,providing an alternative therapeutic approach dual targeting fatty acid metabolism and CTLA-4 in NKTCL.

关 键 词：KILLER METABOLISM LYMPHOMA 

分 类 号：R733.1[医药卫生—肿瘤]