Division of Hematology, Brigham and Women's Hospital, 77 Avenue Louis Pasteur - HIM 770, Boston, MA, 02115, USA.
Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, 700 University Ave., Toronto, ON, M5G1Z5, Canada.
Curr Hematol Malig Rep. 2018 Jun;13(3):202-211. doi: 10.1007/s11899-018-0449-7.
Over the past two decades, the introduction of tyrosine kinase inhibitors (TKIs) has transformed the treatment of chronic myeloid leukemia (CML). With four agents currently approved for frontline use in chronic-phase (CP) disease, it follows that treatment decision-making has been rendered more challenging. Here we will review recent advances that help inform the selection of a first-line TKI.
Extended follow-up of the seminal CML trials has demonstrated the long-term efficacy of TKIs, while also highlighting significant differences in their respective toxicity profiles and potency. Dasatinib and nilotinib generate deeper molecular responses than imatinib, particularly among patients with higher risk disease, but this has not translated into a significant survival advantage. Similar results have been obtained at 1 year with bosutinib; its efficacy and toxicity were well balanced at a dose of 400 mg daily, prompting its recent approval for this indication. Lastly, multiple studies have demonstrated that TKIs can be safely discontinued in select individuals who have maintained deep responses for extended periods, establishing treatment-free remission as a novel goal in CP CML. The careful consideration of parameters such as disease risk, the potency, and toxicity profile of each TKI, as well as each patient's unique comorbidities and preferences, enables truly individualized therapeutic decision-making in CP CML, with the goal of ensuring that a high quality of life accompanies the survival advantage conferred by these agents.
在过去的二十年中，酪氨酸激酶抑制剂（TKI）的引入改变了慢性髓性白血病（CML）的治疗方式。目前有四种药物被批准用于慢性期（CP）疾病的一线治疗，这使得治疗决策更加具有挑战性。在这里，我们将回顾有助于指导一线 TKI 选择的最新进展。
对 CML 关键试验的扩展随访表明了 TKI 的长期疗效，同时也凸显了它们各自在毒性特征和疗效方面的显著差异。达沙替尼和尼洛替尼比伊马替尼产生更深的分子反应，尤其是在高危疾病患者中，但这并没有转化为显著的生存优势。博舒替尼在 1 年时也取得了类似的结果；其 400mg 每日剂量的疗效和毒性平衡良好，促使其最近获得该适应证的批准。最后，多项研究表明，在一些长期保持深度缓解的患者中，可以安全地停用 TKI，确立了无治疗缓解作为 CP CML 的一个新目标。仔细考虑疾病风险、每种 TKI 的疗效和毒性特征以及每位患者的独特合并症和偏好等参数，能够实现 CP CML 的真正个体化治疗决策，目标是确保这些药物带来的生存优势伴随着高质量的生活。
