达沙替尼对中国慢性髓性白血病伊马替尼耐药或不耐受患者疗效及安全性研究

Study on efficiency and safety of dasatinib in Chinese patients with chronic myelogenous leukemia who are resistant or intolerant to imatinib

目的确证达沙替尼在中国慢性髓性白血病（CML）伊马替尼耐药或不耐受的患者中的疗效及安全性。方法119例对伊马替尼耐药或不耐受的CML患者接受达沙替尼治疗，其中慢性期59例、加速期25例、急变期35例。慢性期患者剂量为100mg每日1次，加速期及急变期患者剂量为70mg每日2次，评估患者血液学反应、遗传学反应、无进展生存（PFS）、总生存（Os）以及不良反应情况。结果慢性期、加速期、急变期疗程中位数分别为19．32、20．99及3．22个月。59例慢性期患者的完全血液学缓解（CHR）率为91．5％，获得主要细胞遗传学缓解（MCyR）30例（50．8％），其中25例（42．4％）为完全细胞遗传学缓解（CCyR），达到MCyR的中位时间为12．1周；获得MCyR的慢性期患者无一例出现进展及死亡。25例加速期患者的CHR率、主要血液学缓解（MaHR）率分别为52．0％、84．0％，达到CHR、MaHR的中位时间为16．0、12．1周，获得MCyR10例，其中9例为CCyR．力口速期患者中位PFS期为25．7个月。35例急变期患者的CHR率、MaHR率分别为17．1％、31．4％，达到CHR、MaHR的中位时间均为12．1周；MaHR的中位持续时间为11．2个月；8例急变期患者获得MCyR，MCyR的中位持续时间为13．2个月；急变期患者的中位PFS、OS期分别为4．3、16．7个月。达沙替尼治疗相关的3—4级血液学不良反应常见，但通过剂量调整以及支持治疗可得到有效控制。慢性期患者发生3～4级中性粒细胞（ANC）、血小板减少比例分别为52．5％、61．0％，进展期患者发生率均在80％以上，仅1例进展期患者因为达沙替尼引起的血小板减少而终止治疗。达沙替尼相关的非血液学不良反应主要包括1～2级胸腔积液、头痛、肺炎、腹泻，总体而言进展期患者不良反应发生率高于慢性期患者。结论达沙替尼治疗对伊马替尼耐药或不耐受的各期CML患者可获得相对持久的血液学甚至细胞遗传学缓解且耐受性良好。

Objective To evaluate the efficiency and safety of dasatinib in Chinese patients （pts） with chronic myelogenous leukemia （CML） in chronic phase （CP） , accelerated-phase （AP） or blast-phase （BP） who are resistant or intolerant to imatinih （IM）. Methods 119 CML pts received dasatinib 100 mg once daily for pts in CP or 70 mg twice daily for pts in AP/BP. The hematologic/cytogenetic response, pro- gression-free-survival （PFS）, overall survival （OS） and adverse effects （AE） of the pts were assessed. Re- suits 59 pts in CP, 25 in AP and 35 in BP received dasatinib treatment. The median duration of dasatinib treatment were 19.32, 20.99 and 3.22 months respectively. Complete hematologic response（CHR） , major cytogenetic response （MCyR） and complete cytogenetic response （CCyR） were achieved by 91.5% , 50.8% and 42.4% of pts in CP respectively. The median times to achieving MCyR was 12.1 weeks. None of the pts in CP achieved MCyR progressed or died till to last follow-up. CHR and major hematologic response （MaHR） were achieved by 52.0% and 84.0% of pts in AP, respectively. The median time to CHR and MaHR were 16.0 and 12.1 weeks, respectively. 10 pts in AP achieved MCyR and 9 ＇of them were CCyR. The median du- ration of PFS was 25.7 months for pts in AP. For 35 pts in BP, the rates of CHR and MaHR were 17.1% and 31.4% respectively. Both of the median time to CHR and MaHR were 12.1 weeks and median time of duration of MaHR was 11.2 months. 8 pts in BP achieved MCyR and the median time of duration of MCyR was 13.2 months. The median duration of PFS and OS for the pts in BP were 4.3 and 16.7 months respec- tively. Grade 3 -4 of hematologic AEs related to dasatinib were frequent but manageable by dose interrup- tion/reduction or supportive care. 52.5% and 61.0% of pts in CP experienced grade 3 - 4 of neutropenia and thrombocytopenia. More than 80% pts in AP/BP occurred grade 3 -4 cytopenia. The common non -he- matologic AEs related to dasatinib were including grade 1 -2 pleural effusion, headache, pneumonia and di- arrhea. The frequency of non-hematologic AE was higher in pts with AP/BP than in pts with CP. Conclusion Chinese pts with CML resistant or intolerant to IM treated by dasatinib can achieve relatively sustained he- matologic and even cytogenetic remission and are well tolerated.