Yeung David T, Osborn Michael P, White Deborah L, Branford Susan, Braley Jodi, Herschtal Alan, Kornhauser Michael, Issa Samar, Hiwase Devendra K, Hertzberg Mark, Schwarer Anthony P, Filshie Robin, Arthur Christopher K, Kwan Yiu Lam, Trotman Judith, Forsyth Cecily J, Taper John, Ross David M, Beresford Jennifer, Tam Constantine, Mills Anthony K, Grigg Andrew P, Hughes Timothy P
Department of Haematology, and Department of Genetics and Molecular Pathology and Centre for Cancer Biology, SA Pathology, Adelaide, Australia; Discipline of Medicine, School of Medicine, University of Adelaide, Adelaide, Australia; Australasian Leukemia and Lymphoma Group, Melbourne, Australia;
Department of Haematology, and Discipline of Medicine, School of Medicine, University of Adelaide, Adelaide, Australia; Australasian Leukemia and Lymphoma Group, Melbourne, Australia;
Blood. 2015 Feb 5;125(6):915-23. doi: 10.1182/blood-2014-07-590315. Epub 2014 Dec 17.
The Therapeutic Intensification in De Novo Leukaemia (TIDEL)-II study enrolled 210 patients with chronic phase chronic myeloid leukemia (CML) in two equal, sequential cohorts. All started treatment with imatinib 600 mg/day. Imatinib plasma trough level was performed at day 22 and if <1000 ng/mL, imatinib 800 mg/day was given. Patients were then assessed against molecular targets: BCR-ABL1 ≤10%, ≤1%, and ≤0.1% at 3, 6, and 12 months, respectively. Cohort 1 patients failing any target escalated to imatinib 800 mg/day, and subsequently switched to nilotinib 400 mg twice daily for failing the same target 3 months later. Cohort 2 patients failing any target switched to nilotinib directly, as did patients with intolerance or loss of response in either cohort. At 2 years, 55% of patients remained on imatinib, and 30% on nilotinib. Only 12% were >10% BCR-ABL1 at 3 months. Confirmed major molecular response was achieved in 64% at 12 months and 73% at 24 months. MR4.5 (BCR-ABL1 ≤0.0032%) at 24 months was 34%. Overall survival was 96% and transformation-free survival was 95% at 3 years. This trial supports the feasibility and efficacy of an imatinib-based approach with selective, early switching to nilotinib. This trial was registered at www.anzctr.org.au as #12607000325404.
新发白血病治疗强化（TIDEL）-II研究纳入了210例慢性期慢性髓性白血病（CML）患者，分为两个相等的连续队列。所有患者均开始接受伊马替尼600mg/天治疗。在第22天检测伊马替尼血浆谷浓度，若<1000ng/mL，则给予伊马替尼800mg/天。然后根据分子靶点对患者进行评估：分别在3个月、6个月和12个月时，BCR-ABL1≤10%、≤1%和≤0.1%。队列1中未达到任何靶点的患者剂量增加至伊马替尼800mg/天，3个月后若仍未达到相同靶点，则随后换用尼罗替尼400mg，每日两次。队列2中未达到任何靶点的患者直接换用尼罗替尼，两个队列中不耐受或无反应的患者也如此。2年时，55%的患者仍在接受伊马替尼治疗，30%的患者接受尼罗替尼治疗。3个月时，只有12%的患者BCR-ABL1>10%。12个月时64%的患者达到确认的主要分子反应，24个月时为73%。24个月时MR4.5（BCR-ABL1≤0.0032%）为34%。3年时总生存率为96%，无转化生存率为95%。该试验支持了以伊马替尼为基础、选择性早期换用尼罗替尼的方法的可行性和有效性。该试验在www.anzctr.org.au上注册，注册号为#12607000325404。
