Laganà Alessandro, Scalzulli Emilia, Carmosino Ida, Bisegna Maria Laura, Ielo Claudia, Diverio Daniela, Martelli Maurizio, Breccia Massimo
Hematology, Department of Translational and Precision Medicine, Policlinico Umberto I-Sapienza University, Rome, Italy.
Eur J Haematol. 2025 Oct;115(4):367-379. doi: 10.1111/ejh.70006. Epub 2025 Jun 30.
Treatment free remission (TFR) is a key treatment goal in chronic-phase chronic myeloid leukemia (CP-CML) patients with sustained deep molecular response (DMR). While clinical trials report that approximately 40%-50% of such patients can discontinue tyrosine kinase inhibitors (TKIs) without presenting a molecular relapse (MRec), real-world data remain limited. Optimizing patient selection before TKI discontinuation is crucial for CML management and resource allocation.
We conducted a single-center retrospective study on CP-CML patients who discontinued TKIs to evaluate the rate and duration of successful TFR and to identify factors predictive of MRec. Eligibility required prior TKI treatment ≥ 3 years, a minimum molecular response (MR) of MR4.0 before discontinuation, and subsequent serial MR monitoring. MRec was defined as the loss of major MR (MMR).
Of the 118 consecutive CP-CML patients, 60.2% were on imatinib and 39.8% on 2G-TKIs before attempting TFR. Median TKI treatment duration was 10.6 years, and median stable DMR duration was 6.1 years. After a median follow-up of 72.5 months, 34 patients (28.8%) had an MRec, and estimated MRec-free survival was 79.7% at 6 months and 69.9% overall. Multivariate analysis identified three factors associated with shorter TFR: High-risk Sokal score (HR 2.93, p = 0.018), stable DMR duration before TKI suspension < 5 years (HR 3.63, p = 0.002), and prior unstable DMR (HR 2.47, p = 0.019). The BASE-TFR score, assigning one point per factor, stratified patients into low-risk, intermediate-risk (HR 4.19, p = 0.009) and high-risk (HR 14.06, p < 0.001) for MRec.
TFR is feasible in real-world settings. BASE-TFR score may help to better identify candidates for TKI discontinuation in real-life settings.
对于处于慢性期的慢性髓性白血病（CP-CML）患者，若能实现持续深度分子反应（DMR），则治疗后缓解（TFR）是关键的治疗目标。虽然临床试验报告称，约40%-50%的此类患者在停用酪氨酸激酶抑制剂（TKI）后不会出现分子复发（MRec），但真实世界的数据仍然有限。在停用TKI之前优化患者选择对于慢性髓性白血病的管理和资源分配至关重要。
我们对停用TKI的CP-CML患者进行了一项单中心回顾性研究，以评估成功实现TFR的比率和持续时间，并确定预测MRec的因素。入选标准要求先前接受TKI治疗≥3年，在停药前的最低分子反应（MR）为MR4.0，且随后进行连续的MR监测。MRec定义为主要分子反应（MMR）的丧失。
在118例连续的CP-CML患者中，尝试TFR之前，60.2%的患者使用伊马替尼，39.8%的患者使用第二代TKI。TKI的中位治疗持续时间为10.6年，稳定的DMR中位持续时间为6.1年。在中位随访72.5个月后，34例患者（28.8%）出现MRec，6个月时无MRec的估计生存率为79.7%，总体为69.9%。多变量分析确定了与较短TFR相关的三个因素：高危Sokal评分（HR 2.93，p = 0.018）、TKI停药前稳定的DMR持续时间<5年（HR 3.63，p = 0.002）以及先前不稳定的DMR（HR 2.47，p = 0.019）。BASE-TFR评分根据每个因素赋予1分，将患者分为低风险、中风险（HR 4.19，p = 0.009）和高风险（HR 14.06，p < 0.001）的MRec患者。
在真实世界中，TFR是可行的。BASE-TFR评分可能有助于在现实环境中更好地识别适合停用TKI的患者。
