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接受低剂量酪氨酸激酶抑制剂治疗的慢性粒细胞白血病患者成功维持持续分子反应。

Successful maintenance of a sustained molecular response in CML patients receiving low-dose tyrosine kinase inhibitors.

作者信息

Li Yan, Kuang Pu, Zhu Huanling, Pan Ling, Dong Tian, Lin Ting, Chen Yu, Yang Yunfan

机构信息

Department of Hematology, Institute of Hematology, West China Hospital of Sichuan University, Chengdu, P.R. China.

Department of Internal Medicine, Chengdu Wuhou Likang Hospital, Chengdu, P.R. China.

出版信息

Ther Adv Hematol. 2024 Jun 14;15:20406207241259678. doi: 10.1177/20406207241259678. eCollection 2024.

Abstract

BACKGROUND

The development of tyrosine kinase inhibitor (TKI) therapy has positively impacted the survival rates of patients with chronic myeloid leukemia (CML). It is common in medical practice to adjust the dosage of TKI downward because of TKI-associated adverse events, financial burden, comorbidity, or an attempt at treatment-free remission.

OBJECTIVES

This investigation sought to explore the feasibility of employing a reduced dosage of TKI for treating CML.

DESIGN

This was a retrospective study.

METHODS

Patients with CML in its chronic phase who had been on a reduced dose of TKI for a minimum of 3 months for various reasons in a practical clinical environment, irrespective of molecular response, were included. Regular molecular monitoring was performed, and changes in adverse events were recorded after dose reduction.

RESULTS

This research included a total of 144 participants. Upon reducing the dosage, 136 of 144 patients achieved major molecular response or deeper, and 132 of 144 achieved molecular response 4 (MR4). Following a median observation period of 16 months, the calculated 1- and 2-year survival rates free from MR4 failure were estimated to be 96.5% (95% CI: 90.8-98.7) and 90.5% (95% CI: 81.3-95.3), respectively. MR4 failure-free survival was better in patients with longer MR4 durations (⩾34 months) before dose reduction ( = 0.02). The median interval from dose reduction to MR4 loss was 15 months. Improved TKI-associated adverse events after dose reduction were observed in 61.3% of patients.

CONCLUSION

Lowering the TKI dose can effectively preserve a deep molecular response over time while relieving adverse events caused by TKIs.

摘要

背景

酪氨酸激酶抑制剂(TKI)疗法的发展对慢性髓性白血病(CML)患者的生存率产生了积极影响。在医疗实践中,由于TKI相关的不良事件、经济负担、合并症或尝试无治疗缓解而向下调整TKI剂量是常见的。

目的

本研究旨在探讨采用降低剂量的TKI治疗CML的可行性。

设计

这是一项回顾性研究。

方法

纳入在实际临床环境中因各种原因接受至少3个月低剂量TKI治疗的慢性期CML患者,无论分子反应如何。进行定期分子监测,并记录剂量降低后不良事件的变化。

结果

本研究共纳入144名参与者。降低剂量后,144名患者中有136名达到主要分子反应或更深反应,144名中有132名达到分子反应4(MR4)。中位观察期为16个月后,计算得出的1年和2年无MR4失败生存率估计分别为96.5%(95%CI:90.8 - 98.7)和90.5%(95%CI:81.3 - 95.3)。剂量降低前MR4持续时间较长(⩾34个月)的患者无MR4失败生存率更好(P = 0.02)。从剂量降低到MR4丧失的中位间隔时间为15个月。61.3%的患者在剂量降低后观察到TKI相关不良事件有所改善。

结论

降低TKI剂量可有效长期维持深度分子反应,同时减轻TKI引起的不良事件。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a49/11179506/a6b8f3f9819c/10.1177_20406207241259678-fig1.jpg

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