Ivosidenib in Chinese patients with relapsed or refractory isocitrate dehydrogenase 1 mutated acute myeloid leukemia:a registry study  

作　　者：Mingyuan Sun Qingsong Yin Yang Liang Chunkang Chang Jing Zheng Jian Li Chunyan Ji Huiying Qiu Junmin Li Yuping Gong Sheng Luo Yan Zhang Rumei Chen Zhenwei Shen Zenglian Yue Siyuan Wang Qingmei Shi Jason Yang Jie Jin Jianxiang Wang 

机构地区：[1]State Key Laboratory of Experimental Hematology,National Clinical Research Center for Blood Disease,Institute of Hematology and Blood Diseases Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Tianjin,China [2]Department of Hematology,Henan Cancer Hospital,Zhengzhou,China [3]Department of Hematologic Oncology,State Key Laboratory of Oncology in South China,Collaborative Innovation Center for Cancer Medicine,Sun Yat-sen University Cancer Center,Guangzhou,China [4]Department of Hematology,Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University,Shanghai,China [5]Department of Hematology,Fujian Medical University Union Hospital,Fuzhou,China [6]Department of Hematology,Peking Union Medical College Hospital,Beijing,China [7]Department of Hematology,Qilu Hospital of Shandong University,Jinan,China [8]Department of Hematology,The First Affiliated Hospital of Soochow University,Suzhou,China [9]Department of Hematology,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,China [10]Department of Hematology,West China Hospital of Sichuan University,Chengdu,China [11]Department of Hematology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China [12]CStone Pharmaceuticals(Suzhou)Co.Ltd.,Suzhou,China [13]Department of Hematology,The First Affiliated Hospital,Zhejiang University,School of Medicine,Hangzhou,China

出　　处：《Blood Science》2024年第3期33-41,共9页血液科学（英文）

摘　　要：Ivosidenib,an isocitrate dehydrogenase 1(IDH1)inhibitor,has demonstrated clinical benefits in a pivotal study(AG120-C-001)in patients with IDH1-mutated(mIDH1)acute myeloid leukemia(AML).A registry study(CS3010-101:NCT04176393)was conducted to assess the pharmacokinetic(PK)characteristics,safety,and efficacy of ivosidenib in Chinese patients with relapsed or refractory(R/R)mIDH1 AML.Patients received ivosidenib 500 mg once daily for 28-day cycles until disease progression.Ten subjects underwent intensive PK/progressive disease(PD)assessments.All subjects had the clinical response assessed at screening,every 28 days through month 12,and then every 56 days.Between November 12,2019,and April 2,2021,30 patients were enrolled;26(86.7%)had de novo AML and 18(60.0%)were transfusion-dependent at baseline.Following single and repeated doses of ivosidenib,median time to maximum plasma concentration(T_(max))was 4.0 and 2.0 hours,respectively.The inter-individual variability of pharmacokinetic exposure was moderate to high(coefficient of variation[CV],25%–53%).No obvious accumulation was observed after repeated doses at cycle 2 day 1.Regarding the clinical response,the CR+CRh rate was 36.7%(95%confidence interval[CI]:19.9%–56.1%),the median duration of CR+CRh was 19.7 months(95%CI:2.9 months–not reached[NR]),and median duration of response(DoR)was 14.3 months(95%CI:6.4 months–NR).Consistent clinical benefits and safety of ivosidenib were consistently observed at the final data cutoff with median follow-up time 26.0 months,as compared with primary data cutoff,and the data from Chinese R/R mIDH1 AML patients were also consistent with results from pivotal study.

关 键 词：China IDH1 mutation Ivosidenib Relapsed or refractory acute myeloid leukemia 

分 类 号：R733.71[医药卫生—肿瘤]