Sintilimab(anti-PD-1 antibody)plus chidamide(histone deacetylase inhibitor)in relapsed or refractory extranodal natural killer T-cell lymphoma(SCENT):a phase Ⅰb/Ⅱ study  

作　　者：Yan Gao Haixia He Xueping Li Liling Zhang Wei Xu Ru Feng Wenyu Li Yin Xiao Xinxiu Liu Yu Chen Xiaoxiao Wang Bing Bai Huijing Wu Qingqing Cai Zhiming Li Jibin Li Suxia Lin Yanxia He Liqin Ping Cheng Huang Jiaying Mao Xiujin Chen Baitian Zhao Huiqiang Huang 

机构地区：[1]State Key Laboratory of Oncology in South China&Collaborative Innovation Center of Cancer Medicine,Guangdong Provincial Clinical Research Center for Cancer,Sun Yat-sen University Cancer Center,Guangzhou,China [2]Department of Medical Oncology,Sun Yat-sen University Cancer Center,Guangzhou,China [3]Department of Radiation Oncology,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou,China [4]Department of Hematology,Sun Yat-sen University Cancer Center,Guangzhou,China [5]Cancer Center,Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology,Wuhan,China [6]Department of Hematology,The First Affiliated Hospital of Nanjing Medical University,Jiangsu Province Hospital,Nanjing,China [7]Department of Hematology,Nanfang Hospital,Southern Medical University,Guangzhou,China [8]Department of Lymphoma,Guangdong Provincial People’s Hospital,Guangdong Academy of Medical Sciences,Guangzhou,China [9]Department of pathology,Guangdong General Hospital,Guangdong Academy of Medical Sciences,Guangzhou,China [10]Department of Medical Oncology,Hubei Cancer Center,Wuhan,China [11]Department of Clinical Research,Sun Yat-sen University Cancer Center,Guanzhou,China [12]Department of Pathology,Sun Yat-sen University Cancer Center,Guangzhou,China

出　　处：《Signal Transduction and Targeted Therapy》2024年第6期2765-2773,共9页信号转导与靶向治疗（英文）

基　　金：supported by the National Natural Science Foundation of China(grant numbers 82170188 and 81970176);Guangdong Basic and Applied Basic Research Foundation(grant number 2021A1515110012).

摘　　要：Anti-PD-1 antibodies are a favorable treatment for relapsed or refractory extranodal natural killer T cell lymphoma(RR-ENKTL),however,the complete response(CR)rate and the duration of response(DOR)need to be improved.This phase 1b/2 study investigated the safety and efficacy of sintilimab,a fully human anti-PD-1 antibody,plus chidamide,an oral subtype-selective histone deacetylase inhibitor in 38 patients with RR-ENKTL.Expected objective response rate(ORR)of combination treatment was 80%.Patients received escalating doses of chidamide,administered concomitantly with fixed-dose sintilimab in 21-days cycles up to 12 months.No dose-limiting events were observed,RP2D of chidamide was 30 mg twice a week.Twenty-nine patients were enrolled in phase 2.In the intention-to-treat population(n=37),overall response rate was 59.5% with a complete remission rate of 48.6%.The median DOR,progression-free survival(PFS),and overall survival(OS)were 25.3,23.2,and 32.9 months,respectively.The most common grade 3 or higher treatment-emergent adverse events(AEs)were neutropenia(28.9%)and thrombocytopenia(10.5%),immune-related AEs were reported in 18(47.3%)patients.Exploratory biomarker assessment suggested that a combination of dynamic plasma ctDNA and EBV-DNA played a vital prognostic role.STAT3 mutation shows an unfavorable prognosis.Although outcome of anticipate ORR was not achieved,sintilimab plus chidamide was shown to have a manageable safety profile and yielded encouraging CR rate and DOR in RR-ENKTL for the first time.It is a promising therapeutic option for this population.

关 键 词：KILLER LYMPHOMA doses 

分 类 号：R733.1[医药卫生—肿瘤]