Hochhaus A, Masszi T, Giles F J, Radich J P, Ross D M, Gómez Casares M T, Hellmann A, Stentoft J, Conneally E, García-Gutiérrez V, Gattermann N, Wiktor-Jedrzejczak W, le Coutre P D, Martino B, Saussele S, Menssen H D, Deng W, Krunic N, Bedoucha V, Saglio G
Abteilung Hämatologie/Onkologie, Universitätsklinikum Jena, Jena, Germany.
Department of Haematology and Stem Cell Transplantation St István and St László Hospital, Budapest, Hungary.
Leukemia. 2017 Jul;31(7):1525-1531. doi: 10.1038/leu.2017.63. Epub 2017 Feb 20.
The single-arm, phase 2 ENESTfreedom trial assessed the potential for treatment-free remission (TFR; i.e., the ability to maintain a molecular response after stopping therapy) following frontline nilotinib treatment. Patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase with MR (BCR-ABL1⩽0.0032% on the International Scale (BCR-ABL1)) and ⩾2 years of frontline nilotinib therapy were enrolled. Patients with sustained deep molecular response during the 1-year nilotinib consolidation phase were eligible to stop treatment and enter the TFR phase. Patients with loss of major molecular response (MMR; BCR-ABL1⩽0.1%) during the TFR phase reinitiated nilotinib. In total, 215 patients entered the consolidation phase, of whom 190 entered the TFR phase. The median duration of nilotinib before stopping treatment was 43.5 months. At 48 weeks after stopping nilotinib, 98 patients (51.6%; 95% confidence interval, 44.2-58.9%) remained in MMR or better (primary end point). Of the 86 patients who restarted nilotinib in the treatment reinitiation phase after loss of MMR, 98.8% and 88.4%, respectively, regained MMR and MR by the data cutoff date. Consistent with prior reports of imatinib-treated patients, musculoskeletal pain-related events were reported in 24.7% of patients in the TFR phase (consolidation phase, 16.3%).
单臂2期ENESTfreedom试验评估了一线尼罗替尼治疗后无治疗缓解（TFR，即停止治疗后维持分子反应的能力）的可能性。纳入了处于慢性期的费城染色体阳性慢性髓性白血病患者，这些患者达到主要分子反应（国际量表上BCR-ABL1≤0.0032%）且接受一线尼罗替尼治疗≥2年。在尼罗替尼巩固治疗1年期间有持续深度分子反应的患者有资格停止治疗并进入TFR阶段。在TFR阶段出现主要分子反应丧失（MMR；BCR-ABL1≤0.1%）的患者重新开始使用尼罗替尼。共有215名患者进入巩固阶段，其中190名进入TFR阶段。停止治疗前尼罗替尼的中位使用时长为43.5个月。停止尼罗替尼治疗48周后，98名患者（51.6%；95%置信区间为44.2-58.9%）维持主要分子反应或更好反应（主要终点）。在MMR丧失后治疗重新开始阶段重新开始使用尼罗替尼的86名患者中，截至数据截止日期，分别有98.8%和88.4%的患者恢复了MMR和主要分子反应。与先前关于伊马替尼治疗患者的报告一致，TFR阶段24.7%的患者报告了肌肉骨骼疼痛相关事件（巩固阶段为16.3%）。
