Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Am J Hematol. 2022 Nov;97(11):1413-1418. doi: 10.1002/ajh.26689. Epub 2022 Aug 27.
Low-dose dasatinib is safe and effective in patients with chronic myeloid leukemia in chronic phase (CML-CP). No randomized trials have compared the outcome with standard-dose dasatinib. This study aims to compare the outcome of patients with CML-CP treated with frontline dasatinib 50 versus 100 mg/day. We analyzed 233 patients with newly diagnosed CML-CP treated with low-dose dasatinib (N = 83) or standard-dose dasatinib (N = 150). Propensity score analysis with 1:1 matching was performed and identified 77 patients in each cohort without significant baseline differences. Response rates were reported as the cumulative incidences of complete cytogenetic response, major molecular response (MMR), molecular response (MR)4, and MR4.5. Failure-free survival (FFS), event-free survival (EFS), transformation-free survival (TFS), and overall survival (OS) were also compared. Patients on low-dose dasatinib with suboptimal response by European LeukemiaNet (ELN) 2013 criteria had the option to increase the dose to 100 mg/day. The overall median follow-up time was 60 months. The 3-year MMR rates were 92% and 84% for low-dose and standard-dose dasatinib, respectively (p = .23). Dasatinib 50 mg/day induced higher cumulative incidence of MR4 (77% vs. 66%; p = .04) and MR4.5 (77% vs. 62%; p = .02) at 3 years. The 4-year FFS, EFS and OS rates were 89% versus 77% (p = .04), 95% versus 92% (p = .06), and 97% versus 96% (p = .78) with low-dose and standard-dose dasatinib, respectively. The rate of any grade pleural effusion was 5% with dasatinib 50 mg/day compared to 21% with 100 mg/day. Dasatinib 50 mg/day is at least as effective as 100 mg/day with a better safety profile and drug exposure.
低剂量达沙替尼治疗慢性髓性白血病慢性期（CML-CP）患者安全且有效。目前尚无比较标准剂量达沙替尼与低剂量达沙替尼的随机临床试验。本研究旨在比较一线治疗中低剂量（50mg/d）和标准剂量（100mg/d）达沙替尼治疗 CML-CP 患者的疗效。我们分析了 233 例初诊 CML-CP 患者，其中接受低剂量达沙替尼治疗（N=83）或标准剂量达沙替尼治疗（N=150）。采用倾向评分 1:1 匹配分析，共纳入低剂量达沙替尼组和标准剂量达沙替尼组各 77 例患者，两组基线特征无显著差异。完全细胞遗传学缓解（CCyR）、主要分子学缓解（MMR）、MR4 和 MR4.5 的累积发生率报告为缓解率。无失败生存（FFS）、无事件生存（EFS）、无转化生存（TFS）和总生存（OS）也进行了比较。根据欧洲白血病网络（ELN）2013 标准，对低剂量达沙替尼治疗后未达最佳反应的患者，可增加剂量至 100mg/d。中位随访时间为 60 个月。低剂量达沙替尼组和标准剂量达沙替尼组的 3 年 MMR 率分别为 92%和 84%（p=0.23）。达沙替尼 50mg/d 诱导的 MR4（77% vs. 66%；p=0.04）和 MR4.5（77% vs. 62%；p=0.02）累积发生率在 3 年时更高。低剂量达沙替尼组和标准剂量达沙替尼组的 4 年 FFS、EFS 和 OS 率分别为 89% vs. 77%（p=0.04）、95% vs. 92%（p=0.06）和 97% vs. 96%（p=0.78）。达沙替尼 50mg/d 组的任何级别胸腔积液发生率为 5%，而 100mg/d 组为 21%。达沙替尼 50mg/d 与 100mg/d 相比，疗效相当，但安全性和药物暴露更好。
