初诊慢性髓性白血病患者接受酪氨酸激酶抑制剂治疗现状分析:国内多中心、回顾性真实世界研究  

Treatment status of tyrosine kinase inhibitor for newly-diagnosed chronic myeloid leukemia:a domestic multi-centre retrospective real-world study

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 Hospital,Fuzhou 35000

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》2024年第3期215-224,共10页Chinese Journal of Hematology

基　　金：国家自然科学基金(81970140)。

摘　　要：目的回顾性分析国内初诊慢性髓性白血病(CML)患者接受酪氨酸激酶抑制剂(TKI)治疗现状。方法回顾性收集来自中国27个省市自治区共77个中心自2006年1月至2022年12月期间确诊、年龄≥18岁、确诊后6个月内接受伊马替尼、尼洛替尼、达沙替尼或氟马替尼作为一线治疗且资料相对完整的CML慢性期(CP)和加速期(AP)病例。分析一线TKI选择、目前用药现状、药物转换及原因,接受TKI治疗反应、结局及其影响因素。结果研究最终纳入6893例接受伊马替尼(4906例,71.2%)、尼洛替尼(1157例,16.8%)、达沙替尼(298例,4.3%)或氟马替尼(532例,7.2%)作为一线治疗的成人CML-CP(6453例,93.6%)和AP(440例,6.4%)患者。所有患者中位随访43(IQR 22~75)个月,共1581例(22.9%)患者由于耐药(1055例,15.3%)、不耐受(248例,3.6%)、为追求更好疗效(168例,2.4%)、经济或其他原因(110例,1.6%)换药。AP患者换药比例显著高于CP患者(44.1%对21.5%,P<0.001),且因耐药而转换治疗的比例也显著更高(75.3%对66.1%,P=0.011)。多因素分析显示,男性、低HGB浓度及ELTS评分中/高危组与CP患者较低的细胞遗传学、分子学反应获得率及较差的结局均相关,高WBC、一线接受第二代TKI治疗与较高的治疗反应获得率相关,初诊时携带Ph+附加染色体异常(ACA)与较差的无进展生存(PFS)相关,而Sokal评分中/高危组仅与较低的完全细胞遗传学反应、主要分子学反应获得率和较差的PFS相关;较低的HGB浓度和较大的脾脏与AP患者较低的细胞遗传学和分子学反应获得率相关,一线接受第二代TKI治疗与较高的治疗反应获得率相关,较低的PLT、较高的原始细胞比例和初诊时携带Ph+ACA与较差的无转化生存相关,初诊时携带Ph+ACA与较差的总生存相关。结论目前,绝大多数的初诊CP或AP CML患者可长期获益于TKI治疗,获得较好的治疗反应及生存结局。Objective To retrospectively analyze the treatment status of tyrosine kinase inhibitors(TKI)in newly diagnosed patients with chronic myeloid leukemia(CML)in China.Methods Data of chronic phase(CP)and accelerated phase(AP)CML patients diagnosed from January 2006 to December 2022 from 77 centers,≥18 years old,and receiving initial imatinib,nilotinib,dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated.The choice of initial TKI,current TKI medications,treatment switch and reasons,treatment responses and outcomes as well as the variables associated with them were analyzed.Results 6893 patients in CP(n=6453,93.6%)or AP(n=440,6.4%)receiving initial imatinib(n=4906,71.2%),nilotinib(n=1157,16.8%),dasatinib(n=298,4.3%)or flumatinib(n=532,7.2%)-therapy.With the median follow-up of 43(IQR 22-75)months,1581(22.9%)patients switched TKI due to resistance(n=1055,15.3%),intolerance(n=248,3.6%),pursuit of better efficacy(n=168,2.4%),economic or other reasons(n=110,1.6%).The frequency of switching TKI in AP patients was significantly-higher than that in CP patients(44.1%vs 21.5%,P<0.001),and more AP patients switched TKI due to resistance than CP patients(75.3%vs 66.1%,P=0.011).Multi-variable analyses showed that male,lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients;higher WBC count and initial the second-generation TKI treatment,the higher response rates;Ph+ACA at diagnosis,poor PFS.However,Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS.Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients;initial the second-generation TKI treatment,the higher treatment response rates;lower PLT count,higher blasts and Ph+ACA,poorer TFS;Ph+ACA,poorer OS.Conclusion At present,the vast majority of newl

关 键 词：白血病 髓样 慢性 酪氨酸激酶抑制剂 治疗现状 多中心 真实世界研究 

分 类 号：R73[医药卫生—肿瘤]