伊马替尼耐药或不耐受的 CML 患者更换二代 TKI治疗的疗效观察及相关因素分析

目的：观察伊马替尼耐药或不耐受的慢性髓性白血病(CML)患者更换二代酪氨酸激酶抑制剂(TKI)后的疗效，分析相关因素对疗效的影响。方法随机选取伊马替尼耐药或不耐受而转用二代 TKI(达沙替尼和尼洛替尼)的患者各25例，监测患者3个月或6个月时 BCR/ ABL 融合基因定量结果，分析患者在6个月达到 BCR/ ABL≤10%这一“最佳”疗效与换药原因、换药时分期、换药时血液学缓解状态、换药后依从性之间的关系。结果因耐药或不耐受而换用二代 TKI 的患者6个月达到 BCR/ ABL≤10%分别有16例(41．0%)和9例(81．8%)；转用二代 TKI 时处于慢性期和进展期的患者6个月达到 BCR/ ABL≤10%分别有23例(76．7%)和2例(10．0%)；转用二代 TKI 时未丧失完全血液学缓解(CHR)和丧失 CHR 的患者6个月达到 BCR/ ABL≤10%分别有16例(72．7%)和9例(32．1%)；转用二代TKI 后依从性好和依从性差的患者6个月达到 BCR/ ABL≤10%分别有23例(74．2%)和2例10．5%)。结论伊马替尼耐药或不耐受的 CML 患者改用二代 TKI 药物可取得一定的疗效，且两种二代 TKI 药物(达沙替尼、尼洛替尼)疗效差异无统计学意义。因不耐受而换药的患者的疗效要优于因耐药而换药的患者；换药时处于慢性期的患者的疗效要优于换药时处于进展期的患者；换药时未丧失 CHR 的患者的疗效要优于丧失 CHR 的患者；服用二代 TKI 药物依从性好的患者的疗效要优于依从性差的患者。

The curative effect observation and relevant factors analysis of the second generation TKI drugs after imatinib resistance or intolerance in chronic myeloid leukemia patients

Objective To observe the curative effect of second generation TKI drugs and analyze the influence of relevant factors in chronic myeloid leukemia (CML) patients with imatinib resistance or intolerance. Methods The patients with Imatinib resistance or intolerance and had switched to the second generation TKI drugs, were se-lected randomly 25 each group. Then, monitored their BCR/ ABL fusion gene quantitative results in the 3rd month or 6th month, analyzed the relationship between achieving BCR/ ABL≤10% within 6 months and relevant factors, including the reason, phase and hematologic remission status while changing drug, and the adherence after the changing. Results There were 16 imatinib resistance patients (41. 0% ) and 9 Imatinib intolerance patients (81. 8% ) who had achieved BCR/ ABL≤10% within 6 months after changing. There were 23 patients(76. 7% ) in chronic phase (CP) and 2 patients(10. 0% ) in advanced phase(blastic phase BP or accelerated phase AP) while changing, who had achieved BCR/ ABL≤10% within 6 months. 16 patients(72. 7% ) had changed drug with complete hematologic remission (CHR) and 9 patients(32. 1% ) without CHR, then achieved BCR/ ABL≤10% within 6 months. 23 patients(74. 2% ) with good adherence of the second generation TKI drugs and 2 patients (10. 5% ) with bad adherence, had achieved BCR/ ABL≤10% within 6 months. Conclusion There is a certain effect on imatinib-resistant or intolerant CML patients who have switched to second-generation TKI drugs. And the difference between the efficacy of these two second-generation TKI drugs (Dasatinib, Nilotinib) is not statistically significant. The imatinib intolerance patients get better effect than the imatinib resistance patients. The patients in CP get better effect than the patients in advanced phase, while changing drug, the patients with CHR get better effect than the patients without CHR. The patients with good adherence of the second generation TKI drugs get bet-ter effect than the patients with bad adherence.