氟马替尼与伊马替尼治疗初发慢性髓性白血病慢性期患者的有效性及严重血液学不良反应发生率比较  

To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia

作　　者：张小帅 刘兵城 杜新[3] 张龑莉 许娜[5] 刘晓力[5] 黎纬明[6] 林海[7] 梁蓉 陈春燕[9] 黄健 杨云帆 朱焕玲[11] 潘崚[11] 王晓冬[12] 李国辉 刘卓刚[14] 张延清[15] 刘振芳[16] 胡建达 刘春水[7] 李菲[18] 杨威[14] 孟力 韩艳秋[20] 林丽娥[21] 赵震宇[21] 涂传清[22] 郑彩凤 白炎亮[23] 周泽平[24] 陈苏宁[25] 仇惠英[25] 杨莉洁 孙秀丽[27] 孙慧[28] 周励[29] 刘泽林 王淡瑜 郭健欣[31] 庞丽萍[32] 曾庆曙[33] 索晓慧 张伟华[35] 郑媛君[35] 江倩[1] Zhang Xiaoshuai;Liu Bingcheng;Du Xin;Zhang Yanli;Xu Na;Liu Xiaoli;Li Weiming;Lin Hai;Liang Rong;Chen Chunyan;Huang Jian;Yang Yunfan;Zhu Huanling;Pan Ling;Wang Xiaodong;Li Guohui;Liu Zhuogang;Zhang Yanqing;Liu Zhenfang;Hu Jianda;Liu Chunshui;Li Fei;Yang Wei;Meng Li;Han Yanqiu;Lin Li’e;Zhao Zhenyu;Tu Chuanqing;Zheng Caifeng;Bai Yanliang;Zhou Zeping;Chen Suning;Qiu Huiying;Yang Lijie;Sun Xiuli;Sun Hui;Zhou Li;Liu Zelin;Wang Danyu;Guo Jianxin;Pang Liping;Zeng Qingshu;Suo Xiaohui;Zhang Weihua;Zheng Yuanjun;Jiang Qian(Peking University People’s Hospital,Peking University Institute of Hematology,National Clinical Research Center for Hematologic Disease,Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation,Beijing 100044,China;National Clinical Research Center for Blood Diseases,Institute of Hematology&Blood Diseases Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Tianjin 300020,China;The Second People’s Hospital of Shenzhen,Shenzhen 518035,China;Henan Cancer Hospital,The Affiliated Cancer Hospital of Zhengzhou University,Zhengzhou 450008,China;Nanfang Hospital,Southern Medical University,Guangzhou 510515,China;Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China;First Hospital of Jilin University,Changchun 130021,China;Xijing Hospital,Airforce Military Medical University,Xi’an 710032,China;Qilu Hospital of Shandong University,Jinan 250012,China;The Fourth Affiliated Hospital of Zhejiang University,Hangzhou 322000,China;Institute of Hematology,West China Hospital,Sichuan University,Chengdu 610041,China;Sichuan Academy of Medical Sciences Sichuan Provincial People’s Hospital,Chengdu 610072,China;Xi’an International Medical Center Hospital,Xi’an 710038,China;Shengjing Hospital of China Medical University,Shenyang 110020,China;The Second Affiliated Hospital of Harbin Medical University,Harbin 150086,China;The First Affiliated Hospital of Guangxi Medical University,Nanning 530021,China;Fujian Medical University Union Hospita

机构地区：[1]北京大学人民医院、北京大学血液病研究所、国家血液系统疾病临床医学研究中心,北京100044 [2]中国医学科学院血液病医院(中国医学科学院血液学研究所),天津300020 [3]深圳市第二人民医院,深圳518035 [4]郑州大学附属肿瘤医院、河南省肿瘤医院、河南省血液病研究所,郑州450008 [5]南方医科大学南方医院,广州510515 [6]华中科技大学同济医学院附属协和医院,武汉430022 [7]吉林大学第一医院,长春130021 [8]空军军医大学西京医院,西安710032 [9]山东大学齐鲁医院,济南250012 [10]浙江大学医学院附属第四医院,杭州322000 [11]四川大学华西医院,成都610041 [12]四川省人民医院,成都610072 [13]空军军医大学第二附属医院,西安710038 [14]中国医科大学附属盛京医院,沈阳110020 [15]哈尔滨医科大学附属第二医院,哈尔滨150086 [16]广西医科大学第一附属医院,南宁530021 [17]福建医科大学附属协和医院,福建省血液病研究所,福建省血液病学重点实验室,福州350001 [18]南昌大学第一附属医院,南昌大学淋巴肿瘤疾病研究所,南昌330006 [19]华中科技大学同济医学院附属同济医院,武汉430030 [20]内蒙古医科大学附属医院,呼和浩特010050 [21]海南省人民医院,海口570311 [22]深圳市宝安区人民医院,深圳518101 [23]河南省人民医院,郑州450003 [24]昆明医科大学第二附属医院,昆明650106 [25]苏州大学附属第一医院,江苏省血液研究所,国家血液系统疾病临床医学研究中心,国家卫生健康委员会血栓与止血重点实验室,血液学协同创新中心,苏州215006 [26]西安国际医学中心医院,西安710117 [27]大连医科大学附属第一医院,大连116011 [28]郑州大学第一附属医院血液科,郑州450000 [29]上海交通大学附属瑞金医院,上海200025 [30]华中科技大学协和深圳医院(南山医院),深圳518000 [31]福建医科大学附属第二医院,泉州362000 [32]北京大学深圳�

出　　处：《中华血液学杂志》2023年第9期728-736,共9页Chinese Journal of Hematology

基　　金：国家自然科学基金(81970140)。

摘　　要：目的比较氟马替尼与伊马替尼治疗初发慢性髓性白血病(CML)慢性期患者的治疗反应、结局以及严重血液学不良反应发生率。方法回顾性收集来自国内76个中心自2006年1月至2022年11月期间确诊、年龄≥18岁、确诊后6个月内接受氟马替尼或伊马替尼作为一线治疗且临床资料相对完整的CML慢性期病例。通过倾向性评分匹配(PSM)减少一线酪氨酸激酶抑制剂(TKI)药物选择偏倚,比较两种TKI的治疗反应及结局。结果研究最终纳入4833例接受伊马替尼(4380例)和氟马替尼(453例)作为一线治疗的成人CML慢性期患者。伊马替尼治疗组中位随访54(IQR:31~85)个月,7年完全细胞遗传学反应(CCyR)、主要分子学反应(MMR)、分子学反应4(MR4)和分子学反应4.5(MR4.5)累积获得率分别为95.2%、88.4%、78.3%和63.0%。7年无治疗失败生存(FFS)率、无进展生存(PFS)率和总生存(OS)率分别为71.8%、93.0%和96.9%。氟马替尼治疗组中位随访18(IQR:13~25)个月,2年CCyR、MMR、MR4和MR4.5累积获得率分别为95.4%、86.5%、58.4%和46.6%。2年FFS率、PFS率和OS率分别为80.1%、95.0%和99.5%。PSM分析显示,氟马替尼治疗组患者CCyR、MMR、MR4和MR4.5累积获得率及FFS率均显著高于伊马替尼治疗组患者(P值均<0.001),但两组患者PFS率(P=0.230)和OS率(P=0.268)差异无统计学意义。两组患者Ⅲ级及以上血液学不良反应的发生率相似(氟马替尼对伊马替尼:10.6%对8.0%)。结论氟马替尼治疗初发CML慢性期患者的治疗反应获得率及FFS率均高于伊马替尼,且严重血液学不良反应发生率相似。Objective To analyze and compare therapy responses,outcomes,and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia(CML).Methods Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers,aged≥18 years,and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated.Propensity score matching(PSM)analysis was performed to reduce the bias of the initial TKI selection,and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared.Results A total of 4833 adult patients with CML receiving initial imatinib(n=4380)or flumatinib(n=453)therapy were included in the study.In the imatinib cohort,the median follow-up time was 54[interquartile range(IQR),31–85]months,and the 7-year cumulative incidences of CCyR,MMR,MR4,and MR4.5 were 95.2%,88.4%,78.3%,and 63.0%,respectively.The 7-year FFS,PFS,and OS rates were 71.8%,93.0%,and 96.9%,respectively.With the median follow-up of 18(IQR,13–25)months in the flumatinib cohort,the 2-year cumulative incidences of CCyR,MMR,MR4,and MR4.5 were 95.4%,86.5%,58.4%,and 46.6%,respectively.The 2-year FFS,PFS,and OS rates were 80.1%,95.0%,and 99.5%,respectively.The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR,MMR,MR4,and MR4.5 and higher probabilities of FFS than those receiving the initial imatinib therapy(all P<0.001),whereas the PFS(P=0.230)and OS(P=0.268)were comparable between the two cohorts.The incidence of severe hematologic adverse events(grade≥Ⅲ)was comparable in the two cohorts.Conclusion Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy,whereas the incidence of severe hematologic adverse events was comparable between the

关 键 词：白血病 髓样 慢性 氟马替尼 伊马替尼 疗效 血液学不良反应 

分 类 号：R733.72[医药卫生—肿瘤]