Sorafenib Maintenance After Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia With FLT3-Internal Tandem Duplication Mutation (SORMAIN)
Sorafenib Maintenance After Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia With FLT3-Internal Tandem Duplication Mutation (SORMAIN)
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DOI：
10.1200/jco.19.03345
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发表时间：
2020-09-10
影响因子：
45.3
通讯作者：
Metzelder, Stephan K.
中科院分区：
文献类型：
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作者：
Burchert, Andreas;Bug, Gesine;Metzelder, Stephan K.
尽管接受了异基因造血干细胞移植（HCT），但FMS样酪氨酸激酶3基因（FLT 3-ITD）内部串联重复突变的急性髓系白血病（AML）患者预后差，经常复发，并因AML而死亡。目前尚不清楚使用FLT 3抑制剂（如多靶点酪氨酸激酶抑制剂索拉非尼）的维持治疗是否能改善HCT后的结局。（SORMAIN;德国临床试验注册中心：DRKS 00000591），83例FLT 3-ITD成人患者-HCT后血液学完全缓解的阳性AML患者被随机分配接受多靶点和FLT 3激酶抑制剂索拉非尼（n = 43）或安慰剂治疗24个月（n = 40安慰剂）。无复发生存期（RFS）是本试验的主要终点。复发定义为复发或死亡，无论先发生。结果：中位随访时间为41.8个月，索拉非尼组与安慰剂组复发或死亡的风险比（HR）为0.39（95%CI，0.18至0.85;对数秩P = 0.013）。安慰剂组24个月RFS概率为53.3%（95% CI，0.36 - 0.68），索拉非尼组为85.0%（95% CI，0.70 - 0.93）（HR，0.256; 95% CI，0.10 - 0.65;对数秩P = 0.002）。探索性数据显示，HCT前检测不到的微小残留病（MRD）和HCT后可检测到的MRD的患者从索拉非尼获得最强的获益。结论索拉非尼维持治疗可降低HCT后FLT 3-ITD阳性AML复发和死亡的风险。(C)2020年美国临床肿瘤学会。
PURPOSE Despite undergoing allogeneic hematopoietic stem cell transplantation (HCT), patients with acute myeloid leukemia (AML) with internal tandem duplication mutation in the FMS-like tyrosine kinase 3 gene (FLT3-ITD) have a poor prognosis, frequently relapse, and die as a result of AML. It is currently unknown whether a maintenance therapy using FLT3 inhibitors, such as the multitargeted tyrosine kinase inhibitor sorafenib, improves outcome after HCT.PATIENTS AND METHODSIn a randomized, placebo-controlled, double-blind phase II trial (SORMAIN; German Clinical Trials Register: DRKS00000591), 83 adult patients with FLT3-ITD-positive AML in complete hematologic remission after HCT were randomly assigned to receive for 24 months either the multitargeted and FLT3-kinase inhibitor sorafenib (n = 43) or placebo (n = 40 placebo). Relapse-free survival (RFS) was the primary endpoint of this trial. Relapse was defined as relapse or death, whatever occurred first.RESULTS With a median follow-up of 41.8 months, the hazard ratio (HR) for relapse or death in the sorafenib group versus placebo group was 0.39 (95% CI, 0.18 to 0.85; log-rank P = .013). The 24-month RFS probability was 53.3% (95% CI, 0.36 to 0.68) with placebo versus 85.0% (95% CI, 0.70 to 0.93) with sorafenib (HR, 0.256; 95% CI, 0.10 to 0.65; log-rank P = .002). Exploratory data show that patients with undetectable minimal residual disease (MRD) before HCT and those with detectable MRD after HCT derive the strongest benefit from sorafenib.CONCLUSION Sorafenib maintenance therapy reduces the risk of relapse and death after HCT for FLT3-ITD-positive AML. (C) 2020 by American Society of Clinical Oncology.