中国真实世界慢性髓性白血病患者停用酪氨酸激酶抑制剂的观察研究  

Observational study of chronic myeloid leukemia Chinese patients who discontinued tyrosine kinase inhibitors in the real-world

作　　者：赵慧芳 杨云帆 刘兵城 黎纬明[4] 许娜[5] 刘晓力[5] 江倩[6] 党惠兵[7] 梁立新[8] 张莉 宋永平 Zhao Huifang;Yang Yunfan;Liu Bingcheng;Li Weiming;Xu Na;Liu Xiaoli;Jiang Qian;Dang Huibing;Liang Lixin;Zhang Yanli;Song Yongping(Department of Hematology,Henan Cancer Hospital,the Affiliated Cancer Hospital of Zhengzhou University,Zhengzhou 450008,China;Department of Hematology,Institute of Hematology,West China Hospital,Sichuan University,Chengdu 610041,China;Institute of Hematology&Blood Diseases Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Tianjin 300020,China;Department of Hematology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China;Department of Hematology,Nanfang Hospital,Southern Medical University,Guangzhou 510515,China;Peking University People's Hospital,Peking University Institute of Hematology,National Clinical Research Center for Blood System Diseases,Beijing 100044,China;The First Affiliated Hospital of Nanyang Medical College,Nanyang 473000,China;Department of Hematology,Sanmenxia Central Hospital,Sanmenxia 472000,China)

机构地区：[1]河南省肿瘤医院,郑州大学附属肿瘤医院血液科,郑州450008 [2]四川大学华西医院血液内科,血液病研究所,成都610041 [3]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 [4]华中科技大学同济医学院附属协和医院血液科,武汉430022 [5]南方医科大学南方医院血液科,广州510515 [6]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 [7]南阳医学高等专科学校第一附属医院血液科,南阳473000 [8]三门峡市中心医院血液科,三门峡472000

出　　处：《中华血液学杂志》2022年第8期636-643,共8页Chinese Journal of Hematology

摘　　要：目的观察真实世界中酪氨酸激酶抑制剂(TKI)治疗慢性髓性白血病(CML)停药患者的无治疗缓解(treatment free remission,TFR)情况,及二代TKI在TFR方面是否优于伊马替尼(IM)。方法对来自国内8家血液病治疗中心的自2013年6月至2021年3月期间停用TKI且有明确停药结局和相对完整临床资料的274例CML患者进行回顾性分析,使用单因素分析和多因素Cox比例风险回归模型评估影响CML患者停药后TFR结局的危险因素。结果274例患者,女性140例(51.1%),停药时中位年龄48(9~84)岁。停药前,172例(62.8%)患者应用IM治疗,102例(37.2%)接受过二代TKI治疗,包括73例IM转换二代TKI者和29例一线二代TKI治疗者。转换二代TKI的原因包括:37例因追求TFR在IM治疗获得深层分子学反应(DMR)期间转换二代TKI、7例因IM不良反应不耐受、29例因TKI治疗未达最佳治疗反应。接受过二代TKI者末次应用TKI类型包括:尼洛替尼96例(94.1%),达沙替尼3例(2.9%),氟马替尼2例(2.0%),1例为二代TKI不耐受再次更换为IM治疗。IM治疗组和二代TKI治疗组在确诊时中位年龄、停药时中位年龄、性别、Sokal评分、TKI治疗前是否应用干扰素、TKI治疗至获得DMR中位时间、停药原因等基线特征差异均无统计学意义(P值均>0.05)。停药前TKI中位累积治疗时间(71.5个月对88个月,P<0.001)、末次TKI中位治疗时间(60个月对88个月,P<0.001)、DMR中位持续时间(58个月对66个月,P=0.002),二代TKI治疗组均较IM治疗组显著缩短。停药后中位随访22(6~118)个月,88例(32.1%)患者在中位6(1~91)个月失去主要分子学反应(MMR),其中53例(60.2%)患者在≤6个月内失去MMR,总体的TFR率67.9%,12个月和24个月的累积TFR率分别为70.5%和67.5%。26例(9.5%)患者发生停药综合征。72例(83.7%)重启TKI治疗患者在中位治疗4(1~18)个月再次获得DMR。单因素分析结果显示,停药前应用二代TKI治疗组患者的TFR率显著高于IM治疗组(77.5%对62.2%,Objective This study aimed to observe whether the treatment-free remission(TFR)of second-generation tyrosine kinase inhibitors(TKI)in chronic myeloid leukemia(CML)is better than imatinib(IM).Methods The clinical data of 274 CML patients who discontinued treatment and with complete clinical data were retrospectively studied from June 2013 to March 2021.Using both univariate and multivariate Cox proportional hazards regression models,risk factors influencing TFR outcomes after drug withdrawal in CML patients were assessed.Results A total of 274 patients were enrolled,140 patients were women(51.1%),with a median age of 48(9-84)years at the time of TKI discontinuation.Prior to TKI discontinuation,172(62.8%)patients were treated with IM,and 102(37.2%)had received second-generation TKI treatment,including 73 patients who had shifted from IM to a second-generation TKI and 29 patients who used second-generation TKI as the first-line treatment.The rationale for converting to a second-generation TKI are as follows:37 patients aimed deep molecular response(DMR)to achieve TFR,seven patients changed due to IM intolerance,and 29 patients changed because of failure to achieve the optimal treatment response.The use of the last type of TKI included 96 patients(94.1%)with nilotinib,three patients(2.9%)with dasatinib,and two patients(2%)with flumatinib,including one patient who changed to IM due to second-generation TKI intolerance.No statistical differences were found in the median age at diagnosis and TKI discontinuation,sex,Sokal score,IFN treatment before TKI,median time of TKI treatment to achieve DMR,and the reasons for TKI discontinuation between the second TKI and IM(P>0.05).The median cumulative treatment time of TKI(71.5 months vs 88 months,P<0.001),the last TKI median treatment time(60 months vs 88 months,P<0.001),and the median duration of DMR(58 months vs 66 months,P=0.002)were significantly shorter in the second-generation TKI compared with IM.In the median follow-up of 22(6-118)months after TKI discontinuation,88 pat

关 键 词：停药 二代酪氨酸激酶抑制剂 伊马替尼 白血病 髓样 慢性 无治疗缓解 

分 类 号：R733.72[医药卫生—肿瘤]