The availability and affordability of multiple BCR::ABL1 tyrosine kinase inhibitors (TKIs) beginning in 2000 have changed the prognosis and treatment dynamics in Philadelphia-chromosome (Ph)-positive (or BCR::ABL1-positive) chronic myeloid leukemia (CML) [1,2,3]. Evolving discussions relate to the optimal biologic (lower) dose schedules; frontline versus later-line therapies; management of toxicities versus resistance; the benefit-risk of changing TKIs in patients in good molecular response in order to achieve treatment-free remission (TFR) status; and, with the availability of generic formulations, the cost or treatment value. These issues have been detailed elsewhere [4,5,6].

In the early days, with multiple unanswered questions, the main aims of TKI therapy were borrowed from the experience with interferon alpha. These focused on the achievement of hematologic response and cytogenetic response/complete cytogenetic response (CCyR). The latter endpoint, which required a bone marrow evaluation, was later replaced by its equivalent molecular endpoint, BCR::ABL1 transcripts on the International Scale (IS) of ≤1% (2-log reduction of BCR::ABL1 transcripts, or MR2). The achievement of major molecular response (MMR; BCR::ABL1 transcripts [IS] ≤0.1%), a deeper response than MR2, was later found to correlate with event-free survival (EFS) and has been used as an early surrogate endpoint for EFS improvement in clinical trials.

从 2000 年开始，多种BCR::ABL1酪氨酸激酶抑制剂 (TKI)的可用性和可负担性改变了费城染色体 (Ph) 阳性（或BCR::ABL1阳性）慢性粒细胞白血病 (CML) 的预后和治疗动态[1,2,3]。不断发展的讨论涉及最佳生物（较低）剂量方案；一线治疗与后期治疗；毒性与耐药性的管理；为达到无治疗缓解 (TFR) 状态而对具有良好分子反应的患者改变 TKI 的获益-风险；并且，随着通用制剂的可用性，成本或治疗价值。这些问题已在其他地方详细说明[4,5,6]。

早期，由于存在多个未解答的问题，TKI 治疗的主要目标借鉴了干扰素 α 的经验。这些重点关注血液学反应和细胞遗传学反应/完全细胞遗传学反应（CCyR）的实现。后一个终点需要进行骨髓评估，后来被其等效的分子终点所取代，即国际尺度 (IS) 上的BCR::ABL1转录本≤1%（ BCR::ABL1转录本减少 2 个对数，或 MR2） ）。主要分子缓解（MMR； BCR::ABL1转录本 [IS] ≤0.1%）的实现，比 MR2 更深的缓解，后来发现与无事件生存 (EFS) 相关，并已被用作早期替代终点改善临床试验中的 EFS。