TKI药物换药时机的研究

Research of TKI drugs switching time point

目的探讨TKI类药物的最佳换药时机。方法初诊BCR/ABL阳性的慢性粒细胞白血病慢性期(chronic myelogenous leukemia chronic phase,CML-CP)患者,给予第一代酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKIs)伊马替尼治疗,定期监测BCR/ABL国际标准值(international standard,IS)及融合基因较治疗前基线下降水平(残留值,即治疗后基因数值/治疗前基因数值),据此结果决定药物转换。结果 25例CML-CP患者中,3个月时IS值≤10%且残留值≤10%者18例,占72%,全部在12个月时达到了主要分子学反应(major molecular reaction,MMR,IS≤0.1%);两个数值均>10%者4例,占16%,12个月均未达到MMR;IS值≤10%,但残留值>10%者3例,占12%,12个月时1例达到MMR,2例未达到,均于15个月时更换二代药物—尼洛替尼。结论伊马替尼治疗3个月时IS及残留值均≤10%者继续原治疗;均>10%者需即刻更换二代药物;IS值≤10%但残留值>10%者,根据病人情况决定是否调整药物,如条件允许仍建议尽早换药。

Objective：To analyze the best switching time point of TKI drugs. Methods：The patients diagnosed with BCR/ABL positive and in the chronic myelogenous leukemia chronic phase（ CML-CP）,were treated with the first genera-tion of tyrosine kinase inhibitor. The drug conversion was decided by BCR/ABL international standard（ IS）value and re-sidual value of the fusion gene. Results：There were 25 CML-CP patients. Among them,the number of patients whose IS value was less than or equal to 10% and the residual value that was less than or equal to 10% at the third month was 18 ca-ses,accounting for 72% of all,which all achieved major molecular reaction（ MMR）at the twelfth month. The number of patients whose IS value and residual value were both more than 10% was 4 cases,accounting for 16% of all,and none reached MMR at the twelfth month. There were 3 cases whose IS value was less than or equal to 10% and the residual val-ue was more than 10%,accounting for 12% of all. In these 3 cases,1 case achieved MMR,and 2 cases did not reach MMR who all were replaced with the second generation nilotinib at the fifteenth month. Conclusion：If the IS value and re-sidual value are less than or equal to 10% at the third month treated by imatinib,the original treatment can be kept. If the IS value and residual value are both more than 10%,the second generation nilotinib can be replaced. If the IS value is less than or equal to 10% and the residual value was more than 10%,it depends on the conditions of the patients and it is sug-gested that the drugs be replaced as soon as possible.