South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, SA, Australia.
Hospital Das Clinicas Da UFMG, Belo Horizonte, Brazil.
Leukemia. 2021 Jun;35(6):1631-1642. doi: 10.1038/s41375-021-01260-y. Epub 2021 May 12.
The ENESTop study evaluated treatment-free remission (TFR) in patients with chronic myeloid leukemia (CML) in chronic phase who had received ≥3 years of tyrosine kinase inhibitor therapy and achieved sustained deep molecular response only after switching from imatinib to nilotinib. After 1-year nilotinib consolidation, 126 patients attempted TFR. At 48 weeks (primary analysis), 57.9% (73/126) were in TFR. In the present analysis at 5 years, 42.9% (54/126) were in TFR. Since the 48-week analysis, among patients who left the TFR phase, 58% (11/19) did not have a loss of molecular response and discontinued for other reasons. Of the 59 patients who reinitiated nilotinib upon loss of major molecular response (MMR) or confirmed loss of MR, 98.3% regained MMR, 94.9% regained MR, and 93.2% regained MR. Overall adverse event rates decreased over the 5 years of TFR. In patients reinitiating nilotinib, there was a cumulative increase in cardiovascular events with longer nilotinib exposure. No disease progression or CML-related deaths were reported. Overall, these results confirm the durability and safety of TFR for patients receiving second-line nilotinib. Cardiovascular risk should be carefully managed, particularly when reinitiating treatment after TFR.
ENESTop 研究评估了慢性髓性白血病（CML）慢性期患者在接受 ≥3 年酪氨酸激酶抑制剂治疗并在从伊马替尼转换为尼洛替尼后仅获得持续深度分子缓解的情况下的无治疗缓解（TFR）。在尼洛替尼巩固治疗 1 年后，126 例患者尝试 TFR。在 48 周（主要分析）时，57.9%（73/126）处于 TFR。在本次 5 年分析中，42.9%（54/126）处于 TFR。自 48 周分析以来，在离开 TFR 阶段的患者中，58%（11/19）没有分子反应丧失并因其他原因停药。在失去主要分子反应（MMR）或确认失去 MR 的 59 例患者中，98.3%恢复 MMR，94.9%恢复 MR，93.2%恢复 MR。在 TFR 的 5 年期间，总体不良事件发生率下降。在重新开始使用尼洛替尼的患者中，随着尼洛替尼暴露时间的延长，心血管事件的累积发生率增加。未报告疾病进展或 CML 相关死亡。总的来说，这些结果证实了二线尼洛替尼治疗的患者 TFR 的持久性和安全性。应谨慎管理心血管风险，尤其是在 TFR 后重新开始治疗时。
