2020年中国慢性髓性白血病患者酪氨酸激酶抑制剂治疗状况调研

Treatment status of tyrosine kinase inhibitors in Chinese patients with chronic myeloid leukemia in 2020

目的调查中国慢性髓性白血病(CML)患者的治疗现状。方法横断面研究,2020年4月末至5月中旬,以填写调研问卷的形式在全国范围内调研CML患者,分析酪氨酸激酶抑制剂(TKI)一线选择、目前用药、药物转换和获得主要分子学反应(MMR)的比例及其影响因素。结果2933份来自全国31个省市自治区CML受访者的问卷可供分析,男性1683例(57.4%),中位年龄38(16~87)岁。一线选择:伊马替尼2481例(84.6%),原创性新药(原研药)1803例(61.5%)。填写问卷时用药:伊马替尼1765例(60.2%),原研药1791例(61.1%)。共1185例(40.4%)受访者曾经历TKI药物转换。1944例初发慢性期受访者TKI中位治疗45(3~227)个月,1417例(72.9%)获得≥MMR的疗效。多因素分析显示,城镇户籍(OR=0.6,95%CI 0.5~0.8,P<0.001)、≥大学学历(OR=0.5,95%CI 0.4~0.7,P<0.001)和进展期(OR=0.5,95%CI 0.3~0.8,P=0.001)受访者更少首选仿制TKI,而来自中部地区受访者比东部地区更多首选国产仿制TKI(OR=1.7,95%CI 1.4~2.0,P<0.001)。进展期受访者更多首选二代TKI(OR=5.4,95%CI 3.6~8.2,P<0.001),≥60岁受访者更少首选二代TKI(OR=0.4,95%CI 0.2~0.7,P=0.002)。诊断时处于进展期(OR=2.2,95%CI 1.6~3.2,P<0.001)、首选伊马替尼(OR=2.0,95%CI 1.6~2.6,P<0.001)、首选国产仿制药(OR=1.3,95%CI 1.1~1.6,P=0.002)、诊断距开始TKI治疗的时间更长(OR=1.2,95%CI 1.1~1.2,P<0.001)和服用TKI的时间更长(OR=1.1,95%CI 1.0~1.1,P<0.001)与药物转换比例增高显著相关。城镇户籍(OR=0.7,95%CI 0.6~0.8,P<0.001)、获≥MMR(OR=0.6,95%CI 0.5~0.8,P<0.001)和疗效未知(OR=0.7,95%CI 0.6~0.9,P=0.003)与药物转换比例低显著相关。女性(OR=1.4,95%CI 1.1~1.7,P=0.003)、城镇户籍(OR=1.6,95%CI 1.3~2.0,P<0.001)、初始服用伊马替尼(OR=1.4,95%CI 1.1~1.9,P=0.016)和TKI治疗时间更长(OR=1.2,95%CI 1.2~1.3,P<0.001)与获得≥MMR显著相关,而年龄≥60岁(OR=0.7,95%CI 0.4~1.0,P=0.047)和药物转换(OR=0.6,95%CI 0.5~0.7,P<0.001)与未获得MMR显著相关。结论截至2020年,中国CML患者中大多数首选并持续服用伊马替尼,半数以上服用原研药。社会人口学特征和疾病分期影响了患者的TKI选择、药物转换和治疗反应。

Objective To investigate the current status of treatment choice and responses in patients with chronic myeloid leukemia(CML)in China.Methods From the end of April to mid-May in 2020,a cross-sectional survey,by filling out a survey questionnaire,was conducted to explore the first-line choice of tyrosine kinase inhibitors(TKI),current medications,drug switch and major molecular responses(MMR)as well as the variables associated with them in patients in China.Results Data of 2933 respondents with CML from 31 provinces,municipalities,and autonomous regions across the country were included in this study.1683 respondents(57.4%)were males.Median age was 38(16-87)years old.2481 respondents(84.6%)received imatinib as first-line TKI;1803(61.5%),the original new drug(branded drug).When completing the questionnaire,1765 respondents(60.2%)were receiving imatinib;1791(61.1%),branded drug.1185 respondents(40.4%)had experienced TKI switch.With a median follow-up of 45(3-227)months,1417 of 1944(72.9%)respondents with newly diagnosed CML in the chronic phase achieved MMR.Multivariate analysis showed that the respondents with urban household registration(OR=0.6,95%CI 0.5-0.8,P<0.001),≥bachelor degree(OR=0.5,95%CI 0.4-0.7,P<0.001),and in the advanced phase at diagnosis(OR=0.5,95%CI 0.3-0.8,P=0.001)less preferred Chinese generic TKI,while the respondents from the central region in China more preferred Chinese generic TKI more than those from the eastern region(OR=1.7,95%CI 1.4-2.0,P<0.001).Moreover,the respondents in the advanced phase at diagnosis more preferred second-generation TKI(OR=5.4,95%CI 3.6-8.2,P<0.001);those≥60 years old,less preferred second-generation TKI(OR=0.4,95%CI 0.2-0.7,P=0.002).Being in the advanced phase at diagnosis(OR=2.2,95%CI 1.6-3.2,P<0.001),first-line choice of imatinib(OR=2.0,95%CI 1.6-2.6,P<0.001)or Chinese generic drugs(OR=1.3,95%CI 1.1-1.6,P=0.002),longer interval from diagnose of CML to starting TKI treatment(OR=1.2,95%CI 1.1-1.2,P<0.001)and longer duration of TKI therapy(OR=1.1,95%CI 1.0-1.1,P<0.001)were significantly associated with TKI switch;urban household registration(OR=0.7,95%CI 0.6-0.8,P<0.001),≥MMR(OR=0.6,95%CI 0.5-0.8,P<0.001)and unknown response(OR=0.7,95%CI 0.6-0.9,P=0.003),no TKI switch.Female sex(OR=1.4,95%CI 1.1-1.7,P=0.003),urban household registration(OR=1.6,95%CI 1.3-2.0,P<0.001),front-line imatinib therapy(OR=1.4,95%CI 1.1-1.9,P=0.016)and longer duration of TKI treatment(OR=1.2,95%CI 1.2-1.3,P<0.001)were significantly associated with achieving a MMR or better response;age≥60 years old(OR=0.7,95%CI 0.4-1.0,P=0.047)and TKI switch(OR=0.6,95%CI 0.5-0.7,P<0.001),achieving no MMR.Conclusions By 2020,the majority of Chinese CML patients received imatinib as the fist-line TKI therapy and continue to take it.More than half of TKIs were branded drugs.Socio-demographic characteristics and clinical variables affect their TKI choice,drug switch,and treatment response.