PDF(Pubmed)
Abstract：
With the advent of tyrosine kinase inhibitors (TKIs), the treatment prospects of chronic myeloid leukemia (CML) have changed markedly. This innovation can lengthen the long-term survival of patients suffering from CML. However, long-term exposure to TKIs is accompanied by various adverse events (AEs). The latter affect the quality of life and compliance of patients with CML, and may lead to serious disease progression (and even death). Recently, increasing numbers of patients with CML have begun to pursue a dose optimization strategy. Dose optimization may be considered at all stages of the entire treatment, which includes dose reduction and discontinuation of TKIs therapy. In general, reduction of the TKI dose is considered to be an important measure to reduce AEs and improve quality of life on the premise of maintaining molecular responses. Furthermore, discontinuation of TKIs therapy has been demonstrated to be feasible and safe for about half of patients with a stable optimal response and a longer duration of TKI treatment. This review focuses mainly on the latest research of dose optimization of imatinib, dasatinib, and nilotinib in CML clinical trials and real-life settings. We consider dose reduction in newly diagnosed patients, or in optimal response, or for improving AEs, either as a prelude to treatment-free remission (TFR) or as maintenance therapy in those patients unable to discontinue TKIs therapy. In addition, we also focus on discontinuation of TKIs therapy and second attempts to achieve TFR.
摘要：
随着酪氨酸激酶抑制剂（TKIs）的出现，慢性粒细胞白血病（CML）的治疗前景发生了明显变化。这种创新可以延长患有CML的患者的长期生存。然而,长期暴露于TKIs会伴随各种不良事件(AE).后者影响CML患者的生活质量和依从性,并可能导致严重的疾病进展（甚至死亡）。最近,越来越多的CML患者开始采用剂量优化策略.可以在整个治疗的所有阶段考虑剂量优化，其中包括剂量减少和停止TKIs治疗。总的来说,在维持分子反应的前提下,降低TKI剂量被认为是降低AE和提高生活质量的重要措施。此外，对于约一半具有稳定的最佳反应和更长的TKI治疗持续时间的患者,停用TKIs治疗是可行和安全的.本文主要对伊马替尼剂量优化的最新研究进行综述,达沙替尼,和尼洛替尼在CML临床试验和现实生活中的应用。我们考虑减少新诊断患者的剂量，或者在最佳反应中，或改善AE，作为无治疗缓解（TFR）的前奏，或作为那些无法停止TKIs治疗的患者的维持治疗。此外,我们还将重点放在停止TKIs治疗和实现TFR的第二次尝试上.
