尼洛替尼治疗伊马替尼疗效欠佳的慢性髓性白血病慢性期患者的回顾性临床分析

Retrospective clinical analysis of switching nilotinib to patients with chronic myeloid leukemia in chronic phase with suboptimal response to imatinib

目的比较一线伊马替尼疗效欠佳的慢性髓性白血病慢性期(CML-CP)患者,继续伊马替尼原方案或转换为尼洛替尼治疗后的疗效及安全性。方法收集伊马替尼疗效欠佳的45例患者,分为伊马替尼组22例及尼洛替尼转换组23例,22例伊马替尼组患者继续接受原方案伊马替尼治疗,剂量均为400 mg qd,又将尼洛替尼转换组分为早期尼洛替尼转换组7例,晚期尼洛替尼组转换有16例。尼洛替尼转换组的23例患者接受尼洛替尼的剂量均为400 mg,q12h。所有入组患者首诊时测定Sokal评分,在治疗过程中随访观察定期监测血液学、细胞遗传学及分子学缓解情况(FISH和RQ-PCR),并对患者用药后的基本情况、临床表现及不良反应进行记录。结果转换尼罗替尼治疗3个月时,早期尼洛替尼转换组中国际标准化BCR-ABL1融合基因转录本水平(BCRABL1IS)<10%的患者有5例(71.4%),晚期尼洛替尼转换组BCR-ABL1IS<10%的患者有6例(37.5%),差异无统计学意义(P>0.05)。中位观察6(3~12)个月,尼罗替尼组中有17例(73.9%)获得部分细胞遗传学反应,9例(39.1%)患者获得主要分子学反应。伊马替尼组中有9例(40.9%)获得部分细胞遗传学反应,2例(9.1%)患者获得主要分子学反应,尼洛替尼组部分细胞遗传学反应、主要分子学反应患者优于伊马替尼组(P值分别为0.027、0.020)。45例患者中达到完全细胞遗传学反应的患者与未达到完全细胞遗传学反应相比,Sokal评分偏低(P=0.032)。结论尼洛替尼可使伊马替尼疗效欠佳的CML-CP患者达到更好的疗效,因此需要及时对伊马替尼疗效欠佳的CML-CP患者进行评估后及时更换为尼洛替尼等二代酪氨酸激酶抑制剂。

Objective To assess the clinical efficacy and safety of original scheme or switching to nilotinib in patients with chronic myeloid leukemia in chronic phase(CML-CP)with suboptimal response of first-line imatinib. Methods 45 patients with suboptimal response of imatinib were collected and divided into 22 patients who continued to use original scheme and 23 patients who switched to nilotinib therapy. All the 22 patients of imatinib group received imatinib 400 mg once a day. And the 23 patients of nilotinib group were divided into early switch group and late switch group. Early switch group had 7 patients, late switch group had 16 patients. Both early and late switch to nilotinib group were subsequently to nilotinib 400 mg q12 h. Sokal scores of all the enrolled patients were measured at the first diagnosis. Hematology, cytogenetics and molecular remission(FISH and RQ-PCR)were monitored, and the patients’ basic information, clinical manifestations and adverse reactions were recorded regularly during the treatment. Results After switching to nilotinib for 3 months,there were 5 patients(71.4%)whose BCR-ABL1IS<10% in the early nilotinib switch group, while 6 patients(37.5%)in the late nilotenib switch group.There was no statistical difference(P>0.05).With a median observation period of 6(3~12)months,there were 17(73.9%)patients achieved partial cytogenetic response and 9(39.1%)patients achieved major molecular response in the nilotinib group,there were 9 patients(40.9%)achieved partial cytogenetic response and 2 patients(9.1%)achieved major molecular response in the imatinib group. Patients who achieved partial cytogenetic response and major molecular response in the nilotinib group were more than those in the imatinib group(P values were 0.027 and 0.020, respectively).Sokal scores of 45 patients who had achieved complete cytogenetic response were lower than those who had achieved it(P=0.032).Conclusion Early switch to nitotinib is feasible and effective to patients who didn’t have optimal response to imatinib. It is necessary to assess patients regularly in order to have the proper timing switching patients to nilotinib therapy.