The University of Texas MD Anderson Cancer Center, Houston, Texas.
Cancer. 2020 Jan 1;126(1):67-75. doi: 10.1002/cncr.32504. Epub 2019 Sep 25.
Dasatinib, a potent Bcr-Abl tyrosine kinase inhibitor, is approved for the treatment of chronic-phase chronic myeloid leukemia (CML-CP) in the frontline and salvage settings. Notable side effects include pleural effusions and myelosuppression. Dasatinib at 50 mg daily has previously been reported to be active and better tolerated than the approved 100-mg daily dose. The aim of this study was to update the long-term follow-up results of dasatinib at 50 mg daily as frontline therapy for CML-CP.
Eighty-three patients with newly diagnosed CML-CP received dasatinib at 50 mg daily. Eligibility and response criteria were standards used in previous protocols.
After a minimum follow-up of 12 months, 81 patients were evaluable. Two patients came off the study in less than 3 months. The rates of BCR-ABL1 transcript levels (International Standard) at ≤10% and ≤1% at 3 months were 96% and 77%, respectively. The cumulative rates for a complete cytogenetic response by 6 and 12 months were 77% and 95%, respectively. The cumulative rates for a major molecular response, a molecular response with a 4.0-log reduction, and a molecular response with a 4.5-log reduction by 12 months were 81%, 55%, and 49%, respectively. Twenty-one patients (25%) had treatment interruptions for a median of 13 days (range, 4-64 days). Five patients (6%) developed pleural effusions; 4 of these patients (80%) required a dose reduction. Two patients (2%) failed to achieve any cytogenetic or molecular response and were taken off the study. At a median follow-up of 24 months, none of the patients had disease transformation to an accelerated or blastic phase. The 2-year event-free and overall survival rates were 100%.
These updated results continue to support 50 mg of dasatinib daily as an effective and safe dose for early CML-CP.
达沙替尼是一种强效的 Bcr-Abl 酪氨酸激酶抑制剂，适用于慢性期慢性髓性白血病（CML-CP）的一线和挽救治疗。显著的副作用包括胸腔积液和骨髓抑制。此前报道，达沙替尼每天 50mg 的剂量比批准的 100mg 每天的剂量更有效且更耐受。本研究旨在更新达沙替尼每天 50mg 作为 CML-CP 一线治疗的长期随访结果。
83 例新诊断为 CML-CP 的患者接受达沙替尼每天 50mg 治疗。入组和反应标准是以前方案中使用的标准。
在至少 12 个月的随访后，81 例患者可评估。2 例患者在 3 个月内退出研究。3 个月时 BCR-ABL1 转录水平（国际标准）≤10%和≤1%的患者分别为 96%和 77%。6 个月和 12 个月时完全细胞遗传学反应的累积率分别为 77%和 95%。12 个月时主要分子反应、4.0 对数减少的分子反应和 4.5 对数减少的分子反应的累积率分别为 81%、55%和 49%。21 例（25%）患者因中位 13 天（范围 4-64 天）的治疗中断。5 例（6%）患者发生胸腔积液；其中 4 例（80%）需要剂量减少。2 例（2%）患者未能达到任何细胞遗传学或分子反应而被退出研究。在中位随访 24 个月时，无患者疾病转化为加速期或急变期。2 年无事件生存率和总生存率均为 100%。
这些更新的结果继续支持每天 50mg 达沙替尼作为早期 CML-CP 的有效和安全剂量。
