Tolerability-Adapted Imatinib 800 mg/d Versus 400 mg/d Versus 400 mg/d Plus Interferon-α in Newly Diagnosed Chronic Myeloid Leukemia
Tolerability-Adapted Imatinib 800 mg/d Versus 400 mg/d Versus 400 mg/d Plus Interferon-α in Newly Diagnosed Chronic Myeloid Leukemia
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DOI：
10.1200/jco.2010.32.0598
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发表时间：
2011-04-20
影响因子：
45.3
通讯作者：
Saussele, Susanne
中科院分区：
文献类型：
--
作者：
Hehlmann, Ruediger;Lauseker, Michael;Saussele, Susanne
目的伊马替尼400 mg/d治疗慢性期（CP）慢性粒细胞白血病（CML）效果不理想。优化治疗是warranty.Patients和MethodsIn所有，1,014例新诊断的CP-CML患者被随机分配到伊马替尼800 mg/d（n = 338），伊马替尼400 mg/d（n = 325），或伊马替尼400 mg/d加干扰素α（IFN-α; n = 351）。建议调整剂量以避免更高级别的毒性。第一个主要终点是12个月时的主要分子缓解（MMR）。结果耐受性适应性伊马替尼800 mg/d组12个月时的MMR率高于伊马替尼400 mg/d组（59% [95% CI，53%至65%]对44% [95% CI，37%至50%]; P < .001）或伊马替尼400 mg/d加IFN-α（59%对46% [95% CI，40%至52%]; P = .002）。800 mg/d组的中位剂量为628 mg/d，第4 - 6个月期间的最大剂量为737 mg/d，维持剂量为600 mg/d。所有三种治疗方法均耐受良好，3级和4级不良事件相似。与治疗方法无关，12个月时的MMR显示更好的无进展生存期（99%对94%; P = .0023）和总生存期（99%对93%; P = 0.0011），但在国际范围内，0.1%至< 1%之间无差异，结论伊马替尼对早期CML的治疗是一个优化的方案。早期高剂量治疗，随后迅速适应良好的耐受性，增加了12个月时的MMR率。在第12个月达到MMR与生存率改善直接相关。J Clin Oncol 29：1634-1642. (C)2011年美国临床肿瘤学会
PurposeTreatment of chronic-phase (CP) chronic myeloid leukemia (CML) with imatinib 400 mg/d can be unsatisfactory. Optimization of treatment is warranted.Patients and MethodsIn all, 1,014 newly diagnosed CP-CML patients were randomly assigned to imatinib 800 mg/d (n = 338), imatinib 400 mg/d (n = 325), or imatinib 400 mg/d plus interferon alfa (IFN-alpha; n = 351). Dose adaptation to avoid higher-grade toxicity was recommended. First primary end point was major molecular remission (MMR) at 12 months.ResultsA higher rate of MMR at 12 months occurred with tolerability-adapted imatinib 800 mg/d than with imatinib 400 mg/d (59% [95% CI, 53% to 65%] v 44% [95% CI, 37% to 50%]; P < .001) or imatinib 400 mg/d plus IFN-alpha (59% v 46% [95% CI, 40% to 52%]; P = .002). Median dose in the 800-mg/d arm was 628 mg/d with a maximum dose of 737 mg/d during months 4 to 6 and a maintenance dose of 600 mg/d. All three treatment approaches were well tolerated with similar grade 3 and 4 adverse events. Independent of treatment approach, MMR at 12 months showed better progression-free survival (99% v 94%; P = .0023) and overall survival (99% v 93%; P = .0011) at 3 years when compared with > 1% on the international scale or no MMR but showed no difference in 0.1% to < 1% on the international scale, which closely correlates with complete cytogenetic remission.ConclusionTreatment of early-phase CML with imatinib can be optimized. Early high-dose therapy followed by rapid adaptation to good tolerability increases the rate of MMR at 12 months. Achievement of MMR by month 12 is directly associated with improved survival. J Clin Oncol 29:1634-1642. (C) 2011 by American Society of Clinical Oncology