Iurlo Alessandra, Cattaneo Daniele, Bucelli Cristina, Breccia Massimo
Hematology Division, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy.
Hematology, Department of Translational and Precision Medicine, Sapienza University, Policlinico Umberto 1, 00161 Rome, Italy.
J Clin Med. 2021 Feb 1;10(3):515. doi: 10.3390/jcm10030515.
The chronic myeloid leukemia (CML) therapeutic landscape has dramatically changed with tyrosine kinase inhibitor (TKI) development, which allows a near-normal life expectancy. However, long-term TKI exposure has been associated with persistent adverse events (AEs) which negatively impact on quality of life (QoL) and have the potential to cause significant morbidity and mortality. In clinical practice, TKI dose reduction is usually considered to reduce AEs and improve QoL, but dose optimization could have also another aim, i.e., the achievement and maintenance of cytogenetic and molecular responses. While therapy cessation appeared as a safe option for about half of the patients achieving an optimal response, no systematic assessment of long-term TKI dose de-escalation has been made. The present review is focused on the most recent evidences for TKIs dose modifications in CML clinical studies and in the real-life setting. It will consider TKI dose modifications in newly diagnosed patients, dose reduction for AEs, or in deep molecular response, either as a prelude to treatment-free remission (TFR) or as continuous maintenance therapy in those patients not wishing to attempt TFR. In addition, it will focus on patients not achieving a molecular response deep enough to go to TFR, and for whom dose reduction could be an option to avoid AEs.
随着酪氨酸激酶抑制剂（TKI）的发展，慢性髓性白血病（CML）的治疗格局发生了巨大变化，这使得患者的预期寿命接近正常。然而，长期使用TKI与持续的不良事件（AE）相关，这些不良事件会对生活质量（QoL）产生负面影响，并有导致严重发病和死亡的可能性。在临床实践中，通常考虑降低TKI剂量以减少不良事件并改善生活质量，但剂量优化也可能有另一个目标，即实现并维持细胞遗传学和分子反应。虽然对于约一半达到最佳反应的患者来说，停止治疗似乎是一种安全的选择，但尚未对长期降低TKI剂量进行系统评估。本综述聚焦于CML临床研究及现实环境中TKI剂量调整的最新证据。它将考虑新诊断患者的TKI剂量调整、因不良事件或深度分子反应而进行的剂量降低，这既可以作为无治疗缓解（TFR）的前奏，也可以作为那些不希望尝试TFR的患者的持续维持治疗。此外，它将关注那些未达到足够深度分子反应以进入TFR的患者，对于他们来说，降低剂量可能是避免不良事件的一种选择。
