Hematology Unit, Department of Medical Sciences and Public Health, Businco Hospital, University of Cagliari, Cagliari, Italy.
Hematology, Department of Translational and Precision Medicine, Az. Policlinico Umberto I-Sapienza University, Rome, Italy.
Br J Haematol. 2024 Feb;204(2):434-448. doi: 10.1111/bjh.19269. Epub 2023 Dec 26.
The achievement of treatment-free remission (TFR) has become a significant clinical end-point in the management of patients with chronic myeloid leukaemia (CML), providing an opportunity to discontinue therapy with tyrosine kinase inhibitors (TKIs) while maintaining deep molecular response (DMR). Early studies, such as the French STIM trial, have demonstrated that a portion of patients can maintain DMR after treatment cessation, with rates ranging from 40% to 50%, and most relapses occurring within the first 6 months. Key prognostic factors for successful TFR, including treatment duration, duration of DMR, risk scores, and transcript type, have been identified. Optimal patient selection for TFR remains a challenge, but recent research provides insights into potential strategies to increase TFR eligibility. Evidence suggests that early intervention switching to achieve optimal response, treatment combinations, proactive switch in the case of absence of DMR, dose-optimization and induction-maintenance approach can improve molecular responses and, consequently, enhance TFR eligibility. In this review, we report and discuss all the potential therapeutic strategies that may enhance eligibility for a first attempt at TFR, with a particular emphasis on potential future approaches.
无治疗缓解(TFR)的实现已成为慢性髓性白血病(CML)患者管理的重要临床终点,为停止酪氨酸激酶抑制剂(TKI)治疗同时保持深层分子反应(DMR)提供了机会。早期研究,如法国 STIM 试验,已经表明一部分患者在停止治疗后可以维持 DMR,其比例在 40%到 50%之间,并且大多数复发发生在最初的 6 个月内。成功实现 TFR 的关键预后因素,包括治疗持续时间、DMR 持续时间、风险评分和转录类型,已经确定。最优 TFR 患者选择仍然是一个挑战,但最近的研究为增加 TFR 合格性提供了一些策略。有证据表明,早期干预切换以达到最佳反应、治疗联合、在缺乏 DMR 的情况下主动切换、剂量优化和诱导维持方法可以改善分子反应,从而提高 TFR 合格性。在这篇综述中,我们报告并讨论了所有可能增强首次 TFR 合格性的潜在治疗策略,特别强调了潜在的未来方法。