Results from a randomized trial of salvage chemotherapy followed by lestaurtinib for patients with FLT3 mutant AML in first relapse
Results from a randomized trial of salvage chemotherapy followed by lestaurtinib for patients with FLT3 mutant AML in first relapse
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DOI：
10.1182/blood-2010-08-301796
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发表时间：
2011-03-24
期刊：
影响因子：
20.3
通讯作者：
Smith, B. Douglas
中科院分区：
文献类型：
--
作者：
Levis, Mark;Ravandi, Farhad;Smith, B. Douglas
在一项首次复发的FMS样酪氨酸激酶-3（FLT 3）突变型急性髓性白血病治疗的随机试验中，224例患者接受单独化疗或随后接受80 mg FLT 3抑制剂lehrutinib每日两次。终点包括完全缓解或完全缓解伴血小板不完全恢复（CR/CRp）、总生存期、安全性和耐受性。相关研究包括药代动力学和体内FLT 3抑制分析。来替尼组有29例患者达到CR/CRp，对照组有23例（26% vs 21%; P = 0.35），两组之间的总生存期无差异。在接受来鲁替尼治疗的患者中存在毒性证据，尤其是血浆水平超过20 μ M的患者。在来鲁替尼组中，FLT 3抑制与缓解率高度相关，但仅58%的来鲁替尼治疗患者在第15天达到目标抑制。鉴于本试验中只有如此小比例的患者在体内实现了持续的FLT 3抑制，因此关于FLT 3抑制与化疗联合治疗的疗效的任何结论都是有限的。总体而言，化疗后来他替尼治疗并没有提高首次复发的FLT 3突变急性髓系白血病患者的缓解率或延长生存期。本研究在www.clinicaltrials.gov注册为#NCT00079482。（血。2011;117（12）：3294-3301）
In a randomized trial of therapy for FMS-like tyrosine kinase-3 (FLT3) mutant acute myeloid leukemia in first relapse, 224 patients received chemotherapy alone or followed by 80 mg of the FLT3 inhibitor lestaurtinib twice daily. Endpoints included complete remission or complete remission with incomplete platelet recovery (CR/CRp), overall survival, safety, and tolerability. Correlative studies included pharmacokinetics and analysis of in vivo FLT3 inhibition. There were 29 patients with CR/CRp in the lestaurtinib arm and 23 in the control arm (26% vs 21%; P = .35), and no difference in overall survival between the 2 arms. There was evidence of toxicity in the lestaurtinib-treated patients, particularly those with plasma levels in excess of 20 mu M. In the lestaurtinib arm, FLT3 inhibition was highly correlated with remission rate, but target inhibition on day 15 was achieved in only 58% of patients receiving lestaurtinib. Given that such a small proportion of patients on this trial achieved sustained FLT3 inhibition in vivo, any conclusions regarding the efficacy of combining FLT3 inhibition with chemotherapy are limited. Overall, lestaurtinib treatment after chemotherapy did not increase response rates or prolong survival of patients with FLT3 mutant acute myeloid leukemia in first relapse. This study is registered at www.clinicaltrials.gov as #NCT00079482. (Blood. 2011;117(12): 3294-3301)