University of California at San Francisco School of Medicine, San Francisco, CA;
Blood. 2014 Apr 10;123(15):2317-24. doi: 10.1182/blood-2013-10-532341. Epub 2014 Feb 25.
We present long-term follow-up of a dasatinib phase 3 study of patients with imatinib-resistant/-intolerant chronic myeloid leukemia (CML). In the CA180-034 study, 670 patients with imatinib-resistant/-intolerant CML in chronic phase (CML-CP) received dasatinib 100 mg once daily, 50 mg twice daily, 140 mg once daily, or 70 mg twice daily. At 6 years, 188 (28%) of 670 patients remained on study treatment. Estimated 6-year protocol-defined progression-free survival (PFS) rates were 49%, 51%, 40%, and 47%, respectively, and estimated 6-year overall survival (OS) rates were 71%, 74%, 77%, and 70%, respectively (intent-to-treat population, including protocol-defined progression or death after discontinuation). Estimated 6-year rates of survival without transformation on study treatment were 76%, 80%, 83%, and 74%, respectively. Major molecular response was achieved in 43% (100 mg once daily) and 40% (all other arms) of patients by 6 years. Molecular and cytogenetic responses at 3 and 6 months were highly predictive of PFS and OS. Notably, estimated 6-year PFS rates based on ≤1%, >1% to 10%, and >10% BCR-ABL transcripts at 3 months were 68%, 58%, and 26%, respectively. Most adverse events occurred by 2 years. Imatinib-resistant/-intolerant patients with CML-CP can experience long-term benefit with dasatinib therapy, particularly if achieving BCR-ABL ≤10% at 3 months. This study was registered at ClinicalTrials.gov: NCT00123474.
我们呈现了达沙替尼治疗伊马替尼耐药/不耐受慢性髓性白血病（CML）的 3 期研究的长期随访结果。在 CA180-034 研究中，670 例伊马替尼耐药/不耐受的慢性期 CML（CML-CP）患者接受了达沙替尼 100 mg 每日一次、50 mg 每日两次、140 mg 每日一次或 70 mg 每日两次治疗。6 年时，670 例患者中有 188 例（28%）仍在接受研究治疗。估计 6 年的方案定义无进展生存（PFS）率分别为 49%、51%、40%和 47%，估计 6 年的总生存（OS）率分别为 71%、74%、77%和 70%（意向治疗人群，包括停药后方案定义的进展或死亡）。估计 6 年的研究治疗期间无转化生存比例分别为 76%、80%、83%和 74%。43%（100 mg 每日一次）和 40%（所有其他治疗组）的患者在 6 年时达到了主要分子缓解。3 个月和 6 个月时的分子和细胞遗传学反应高度预测 PFS 和 OS。值得注意的是，3 个月时 BCR-ABL 转录物≤1%、>1%~10%和>10%的患者 6 年 PFS 率分别为 68%、58%和 26%。大多数不良事件发生在 2 年内。达沙替尼治疗伊马替尼耐药/不耐受的 CML-CP 患者可获得长期获益，特别是在 3 个月时达到 BCR-ABL≤10%的患者。本研究在 ClinicalTrials.gov 注册：NCT00123474。
