Long-term outcomes with tyrosine kinase inhibitors (TKIs) show that their impact on chronic myeloid leukemia (CML) is sustained as shown by 13 studies with 5- to 14-year-follow-up, and numerous shorter-term studies of newly diagnosed chronic-phase CML. Twenty-five years of imatinib (IM) treatment confirm its beneficial effect on survival and possible cure of CML. Large, randomized, academic, treatment-optimization studies have confirmed and extended the pivotal International Randomized Study on Interferon and STI571. The 3 academic trials in Germany, France, and the United Kingdom did not show benefit of the IM-interferon (IFN) combination, despite the immunomodulatory properties of IFN. Second-generation (2G) TKIs induce responses faster than IM and recognize IM-resistance mutations but do not prolong survival compared with IM. Adverse drug-related reactions (ADRs) limit the general use of 2GTKIs despite frequent but mostly mild IM-ADRs. Molecular monitoring of treatment efficacy has been established serving as an example for other neoplasms. Comorbidities, transcript type, and the negative impact of high-risk additional chromosomal abnormalities were addressed. A new prognostic score (European Treatment and Outcome Study long-term survival score) accounts for the fact that the majority of patients with CML die of other causes. Non-CML determinants of survival have been identified. Large and long-term observational studies demonstrate that progress with CML management has also reached routine care in most but not all instances. Despite merits of 2GTKIs, IM remains the preferred treatment option for CML because of its efficacy and superior safety.

中文翻译：

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酪氨酸激酶抑制剂在慢性粒细胞白血病中的长期结局


酪氨酸激酶抑制剂 （TKI） 的长期结局表明，它们对慢性粒细胞白血病 （CML） 的影响是持续的，如 13 项随访 5 至 14 年的研究以及许多针对新诊断的慢性期 CML 的短期研究所示。伊马替尼 （IM） 治疗 25 年证实了其对 CML 生存和可能治愈的有益影响。大型、随机、 学术、治疗优化研究证实并扩展了关于干扰素和 STI571 的关键国际随机研究。尽管 IFN 具有免疫调节特性，但在德国、法国和英国进行的 3 项学术试验并未显示 IM-干扰素 （IFN） 组合的益处。第二代 （2G） TKI 比 IM 更快地诱导反应并识别 IM 耐药突变，但与 IM 相比不会延长生存期。药物相关不良反应 （ADRs） 限制了 2GTKI 的一般使用，尽管 IM-ADR 频繁但大多是轻微的。治疗效果的分子监测已经建立起来，作为其他肿瘤的一个例子。解决了合并症、转录本类型和高风险额外染色体异常的负面影响。新的预后评分 （European Treatment and Outcome Study long-term survival score） 解释了大多数 CML 患者死于其他原因的事实。已经确定了非 CML 生存决定因素。大型和长期观察性研究表明，CML 管理的进展也已达到大多数但不是所有情况下的常规护理。尽管 2GTKI 有优点，但由于其疗效和卓越的安全性，IM 仍然是 CML 的首选治疗选择。