一线尼洛替尼治疗慢性期慢性髓性白血病患者的持久无治疗缓解：ENESTfreedom 研究的 96 周更新。

Durable treatment-free remission in patients with chronic myeloid leukemia in chronic phase following frontline nilotinib: 96-week update of the ENESTfreedom study.

机构信息

Division of Haematology, SA Pathology, Room 6E359, Royal Adelaide Hospital, 1 Port Rd, Adelaide, SA, 5000, Australia.

Semmelweis University, Budapest, Hungary.

出版信息

J Cancer Res Clin Oncol. 2018 May;144(5):945-954. doi: 10.1007/s00432-018-2604-x. Epub 2018 Feb 22.

PURPOSE

ENESTfreedom is evaluating treatment-free remission (TFR) following frontline nilotinib in patients with chronic myeloid leukemia (CML) in chronic phase. Following our primary analysis at 48 weeks, we here provide an updated 96-week analysis.

METHODS

Attempting TFR required ≥ 3 years of nilotinib, a molecular response of MR [BCR-ABL1 ≤ 0.0032% on the International Scale (BCR-ABL1)], and sustained deep molecular response (DMR) during a 1-year consolidation phase. Patients restarted nilotinib following loss of major molecular response (MMR; BCR-ABL1 ≤ 0.1%).

RESULTS

Ninety-six weeks after stopping treatment (3.6-year median prior nilotinib duration), 93 of 190 patients (48.9%) remained in TFR. Of 88 patients who restarted nilotinib following loss of MMR, 87 regained MMR and 81 regained MR by the data cut-off. Ninety-six-week TFR rates were 61.3, 50.0, and 28.6% in patients with low, intermediate, and high Sokal risk scores at diagnosis, respectively. Patients consistently in MR during consolidation had higher TFR rates (50.6%) than patients with ≥ 1 assessment without MR during consolidation (35.0%). In a landmark analysis, 96-week TFR rates for patients with MR, MR (BCR-ABL1 ≤ 0.01%) but not MR, and MMR but not MR at TFR week 12 were 82.6, 23.1, and 0%, respectively. There were no reports of disease progression or death due to CML; overall adverse event frequency decreased following TFR. Within the follow-up period, TFR did not adversely affect disease outcomes.

CONCLUSIONS

These results demonstrate the feasibility and durability of TFR following frontline nilotinib and emphasize the importance of sustained DMR for TFR.

目的

ENESTfreedom 正在评估一线尼洛替尼治疗慢性期慢性髓性白血病（CML）患者的无治疗缓解（TFR）。在我们的 48 周主要分析之后，我们在此提供更新的 96 周分析。

方法

尝试 TFR 需要尼洛替尼治疗至少 3 年，分子学反应为 MR [国际标准（BCR-ABL1）<0.0032%]，并且在 1 年巩固期期间持续深度分子反应（DMR）。患者在主要分子反应（BCR-ABL1≤0.1%）丧失后重新开始使用尼洛替尼。

结果

停止治疗 96 周后（尼洛替尼治疗前中位数 3.6 年），190 名患者中的 93 名（48.9%）仍处于 TFR。在失去 MMR（BCR-ABL1≤0.1%）后重新开始使用尼洛替尼的 88 名患者中，87 名患者在数据截止时恢复了 MMR，81 名患者恢复了 MR。诊断时低、中、高危 Sokal 风险评分患者的 96 周 TFR 率分别为 61.3%、50.0%和 28.6%。在巩固期内持续处于 MR 的患者 TFR 率（50.6%）高于巩固期内至少有一次评估无 MR 的患者（35.0%）。在一个里程碑分析中，TFR 周 12 时处于 MR、MR（BCR-ABL1≤0.01%）但非 MR、MMR 但非 MR 的患者的 96 周 TFR 率分别为 82.6%、23.1%和 0%。没有因 CML 而发生疾病进展或死亡的报告；TFR 后整体不良事件发生率下降。在随访期间，TFR 并未对疾病结局产生不利影响。