Division of Hematology and Hematologic Malignancies, Department of Internal Medicine, and Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112-5550, USA.
Leukemia. 2012 Feb;26(2):214-24. doi: 10.1038/leu.2011.217. Epub 2011 Aug 16.
In patients with chronic myeloid leukemia (CML), disease in the initial chronic phase (CP) and subsequent progression are driven by the oncogenic activity of the BCR-ABL fusion kinase. Imatinib, a tyrosine kinase inhibitor of BCR-ABL, has been the mainstay of first-line therapy for CML for 10 years. Although patients with CML-CP respond well to imatinib, those who have delayed reductions in leukemic burden during imatinib therapy, such as not achieving a complete cytogenetic response (CCyR) by 12 months, have an increased risk of disease progression. It has been recognized, with 8 years of observation, that patients who achieve an early major molecular response (MMR) on imatinib have a very low probability of disease progression. Recent randomized phase 3 trials have shown that first-line treatment with dasatinib or nilotinib-more potent BCR-ABL inhibitors-results in significantly higher rates and more rapid achievement of CCyR and MMR in comparison with standard-dose imatinib. These trials suggest that CML treatment can be improved with more potent BCR-ABL inhibition during initial therapy, but further follow-up is needed to confirm that the improved response rates with dasatinib and nilotinib are maintained long term.
在慢性髓性白血病（CML）患者中，疾病在初始慢性期（CP）和随后的进展是由 BCR-ABL 融合激酶的致癌活性驱动的。伊马替尼是一种 BCR-ABL 的酪氨酸激酶抑制剂，已成为 CML 一线治疗的主要药物已有 10 年。尽管 CML-CP 患者对伊马替尼反应良好，但那些在伊马替尼治疗期间白血病负荷延迟减少的患者，例如在 12 个月时未达到完全细胞遗传学缓解（CCyR），则疾病进展的风险增加。经过 8 年的观察，已经认识到在伊马替尼上早期达到主要分子反应（MMR）的患者疾病进展的可能性极低。最近的随机 3 期试验表明，与标准剂量的伊马替尼相比，一线使用达沙替尼或尼罗替尼（更有效的 BCR-ABL 抑制剂）治疗可显著提高 CCyR 和 MMR 的获得率和速度。这些试验表明，在初始治疗期间使用更有效的 BCR-ABL 抑制可以改善 CML 的治疗效果，但需要进一步随访以确认达沙替尼和尼罗替尼的改善反应率是否可以长期维持。
