Department of Hematology, Nephrology and Rheumatology, Akita University Graduate School of Medicine
Department of Oncology and Hematology, Jikei University Kashiwa Hospital.
Haematologica. 2018 Nov;103(11):1835-1842. doi: 10.3324/haematol.2018.194894. Epub 2018 Jul 5.
The purpose of this trial was to evaluate the efficacy of 2-year consolidation therapy with nilotinib, at a dose of 300 mg twice daily, for achieving treatment-free remission in chronic myeloid leukemia patients with a deep molecular response ( ≤0.0032%). Successful treatment-free remission was defined as no confirmed loss of deep molecular response. We recruited 96 Japanese patients, of whom 78 sustained a deep molecular response during the consolidation phase and were therefore eligible to discontinue nilotinib in the treatment-free remission phase; of these, 53 patients (67.9%; 95% confidence interval: 56.4-78.1%) remained free from molecular recurrence in the first 12 months. The estimated 3-year treatment-free survival was 62.8%. Nilotinib was readministered to all patients (n=29) who experienced a molecular recurrence during the treatment-free remission phase. After restarting treatment, rapid deep molecular response returned in 25 patients (86.2%), with 50% of patients achieving a deep molecular response within 3.5 months. Tyrosine kinase inhibitor withdrawal syndrome was reported in 11/78 patients during the early treatment-free remission phase. The treatment-free survival curve was significantly better in patients with undetectable molecular residual disease than in patients without (3-year treatment-free survival, 75.6 48.6%, respectively; =0.0126 by the log-rank test). There were no significant differences in treatment-free survival between subgroups based on tyrosine kinase inhibitor treatment before the nilotinib consolidation phase, tyrosine kinase inhibitor-withdrawal syndrome, or absolute number of natural killer cells. The results of this study indicate that it is safe and feasible to stop tyrosine kinase inhibitor therapy in patients with chronic myeloid leukemia who have achieved a sustained deep molecular response with 2 years of treatment with nilotinib. This study was registered with UMIN-CTR (UMIN000005904).
本试验旨在评估每日两次、每次 300 毫克尼洛替尼巩固治疗 2 年，能否使获得深度分子学应答（≤0.0032%）的慢性髓性白血病患者实现无治疗缓解。成功的无治疗缓解定义为未确认深度分子学应答丢失。我们招募了 96 名日本患者，其中 78 名患者在巩固期保持深度分子学应答，因此有资格在无治疗缓解期停止尼洛替尼治疗；其中 53 名患者（67.9%；95%置信区间：56.4-78.1%）在第 12 个月时仍未出现分子学复发。3 年无治疗生存率估计为 62.8%。所有在无治疗缓解期发生分子学复发的患者（n=29）均重新开始尼洛替尼治疗。重新开始治疗后，25 例患者（86.2%）迅速恢复深度分子学应答，其中 50%的患者在 3.5 个月内达到深度分子学应答。11/78 例患者在早期无治疗缓解期出现酪氨酸激酶抑制剂停药综合征。无残留疾病患者的无治疗生存曲线明显优于无残留疾病患者（3 年无治疗生存率，分别为 75.6%和 48.6%；对数秩检验=0.0126）。根据尼洛替尼巩固治疗前的酪氨酸激酶抑制剂治疗、酪氨酸激酶抑制剂停药综合征或自然杀伤细胞绝对数，无治疗生存亚组之间无显著差异。这项研究的结果表明，对于持续获得深度分子学应答、接受尼洛替尼治疗 2 年的慢性髓性白血病患者，停止酪氨酸激酶抑制剂治疗是安全可行的。这项研究在 UMIN-CTR（UMIN000005904）注册。
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