Initial Molecular Response at 3 Months May Predict Both Response and Event-Free Survival at 24 Months in Imatinib-Resistant or -Intolerant Patients With Philadelphia Chromosome-Positive Chronic Myeloid Leukemia in Chronic Phase Treated With Nilotinib
Initial Molecular Response at 3 Months May Predict Both Response and Event-Free Survival at 24 Months in Imatinib-Resistant or -Intolerant Patients With Philadelphia Chromosome-Positive Chronic Myeloid Leukemia in Chronic Phase Treated With Nilotinib
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DOI：
10.1200/jco.2011.40.5217
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发表时间：
2012-12-10
影响因子：
45.3
通讯作者：
Mueller, Martin C.
中科院分区：
文献类型：
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作者：
Branford, Susan;Kim, Dong-Wook;Mueller, Martin C.
目的检查初始分子反应与尼洛替尼长期结局之间的关联。患者和方法纳入 II 期尼洛替尼注册研究中患有伊马替尼耐药或不耐受的慢性粒细胞白血病患者，并进行基线后 BCR-ABL1 转录本评估（N = 237）。结果 3 个月时的 BCR-ABL1 转录本水平（国际量表 [IS]）与完全细胞遗传学反应（CCyR）相关24个月。 BCR-ABL1 (IS) > 1% 至 10% (53% vs 16%) 的患者。 3 个月时的 BCR-ABL1 (IS) 预测 24 个月时的主要分子反应 (MMR)。对于 BCR-ABL1 (IS) > 0.1% 至 1% 至 10% 的患者，24 个月时 MMR 的累积发生率分别为 65%、27% 和 9%。在有或没有基线 BCR-ABL1 突变的患者以及伊马替尼耐药或不耐受的患者中观察到了这些差异。 24 个月时的估计无事件生存 (EFS) 率随着 3 个月时转录水平的升高而降低； BCR-ABL1 (IS) 为 1% 至 10% 的患者。结论 与 BCR-ABL1 (IS) 为 1% 至 10% 的患者相比，3 个月时 BCR-ABL1 (IS) > 10% 的患者 CCyR 和 MMR 累积发生率较低，EFS 率较低。
PurposeThe association between initial molecular response and longer-term outcomes with nilotinib was examined.Patients and MethodsPatients with imatinib-resistant or -intolerant chronic myeloid leukemia in chronic phase from the phase II nilotinib registration study with available postbaseline BCR-ABL1 transcript assessments were included (N = 237).ResultsBCR-ABL1 transcript levels (International Scale [IS]) at 3 months correlated with complete cytogenetic response (CCyR) by 24 months. Patients with BCR-ABL1 (IS) of > 1% to 10% (53% v 16%). BCR-ABL1 (IS) at 3 months predicted major molecular response (MMR) by 24 months. Cumulative incidence of MMR by 24 months for patients with BCR-ABL1 (IS) of > 0.1% to 1% to 10% was 65%, 27%, and 9%, respectively. These differences were observed for patients with or without baseline BCR-ABL1 mutations and for those with imatinib resistance or intolerance. Estimated event-free survival (EFS) rates at 24 months decreased with higher transcript levels at 3 months; patients with BCR-ABL1 (IS) of 1% to 10%.ConclusionPatients with BCR-ABL1 (IS) of > 10% at 3 months had a lower cumulative incidence of CCyR and MMR and lower rates of EFS versus patients with BCR-ABL1 (IS) of