Abstract：
Over the past several years, advances in research, treatment, and market dynamics have impacted treatment strategies in chronic myeloid leukemia in chronic phase (CML-CP). They include the broader availability of cost-effective generic imatinib, and soon other generic second-generation tyrosine kinase inhibitors (TKIs). Access to affordable generics means that all patients with CML-CP should have access to safe and highly effective lifelong therapies. When overall survival is the treatment endpoint, imatinib provides a good treatment value. Second-generation TKIs may be the best frontline strategy when treatment-free remission is the goal. Recent studies have shown maintained efficacy and reduced toxicity when TKIs are used at reduced dosing. Reduced-dose schedules of second-generation TKIs (which are less toxic and induce faster deep molecular responses) may render generic second-generation TKIs a more attractive treatment option. Adjusting the dose of TKI in the presence of mild-to-moderate, or even severe but reversible, adverse events may be preferable to switching to a different TKI. The selection of second-line and beyond therapies depends on the evolving patterns observed with frontline treatment. Dose-adjusted ponatinib schedules have demonstrated improved efficacy and safety in patients resistant to second-generation TKIs or those with T315I-mutated disease. For asciminib, longer-term follow-up is needed to better evaluate its safety and efficacy compared with ponatinib. Allogeneic stem cell transplantation represents a valid alternative to newer-generation TKIs, with a better treatment value when TKIs are priced at >$40,000/year.
摘要：
在过去的几年里，研究进展，治疗,和市场动态影响了慢性粒细胞白血病慢性期（CML-CP）的治疗策略。它们包括更广泛的具有成本效益的仿制药伊马替尼，以及其他通用的第二代酪氨酸激酶抑制剂（TKIs）。获得负担得起的仿制药意味着所有CML-CP患者都应该获得安全有效的终身治疗。当总生存期是治疗终点时，伊马替尼提供了良好的治疗价值。当免治疗缓解为目标时，第二代TKIs可能是最佳的前线策略。最近的研究表明，当TKIs以减少的剂量使用时，保持了疗效并降低了毒性。第二代TKIs的减少剂量时间表（毒性较低并诱导更快的深层分子反应）可能使通用第二代TKIs成为更具吸引力的治疗选择。在轻度至中度的情况下调整TKI的剂量，甚至严重但可逆的，不良事件可能比切换到不同的TKI更可取。二线和其他疗法的选择取决于一线治疗观察到的不断发展的模式。剂量调整的ponatinib方案在第二代TKIs耐药患者或T315I突变疾病患者中显示出改善的疗效和安全性。对于阿西替尼，与普纳替尼相比,需要进行更长期的随访,以更好地评估其安全性和有效性.同种异体干细胞移植代表了新一代TKIs的有效替代方案，当TKI的价格>40,000美元/年时，具有更好的治疗价值。
