Letermovir Prophylaxis for Cytomegalovirus in Hematopoietic-Cell Transplantation
Letermovir Prophylaxis for Cytomegalovirus in Hematopoietic-Cell Transplantation
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DOI：
10.1056/nejmoa1706640
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发表时间：
2017-12-21
影响因子：
158.5
通讯作者：
Badshah, C.
中科院分区：
文献类型：
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作者：
Marty, F. M.;Ljungman, P.;Badshah, C.
巨细胞病毒（CMV）感染仍然是异基因造血细胞移植后常见的并发症。莱特莫韦是一种抗病毒药物，抑制CMV-terminase complex. METHODS在这个3期，双盲试验中，我们随机分配CMV血清阳性移植受体，18岁或以上，在2：1的比例接受莱特莫韦或安慰剂，口服或静脉注射，通过移植后14周;随机化分层根据试验地点和CMV疾病的风险。莱特莫韦以每天480 mg的剂量给药（或在服用环孢菌素的患者中每天240 mg）。发生具有临床意义的CMV感染（CMV疾病或导致抢先治疗的CMV病毒血症）的患者中止试验方案并接受抗CMV治疗。主要终点是在随机分组时未检测到CMV DNA的患者中，移植后24周内发生临床显著CMV感染的患者比例。在第24周中止试验或缺失终点数据的患者被插补为发生主要终点事件。从2014年6月至2016年3月，共有565名患者接受随机分组，并在移植后中位数9天开始接受莱特莫韦或安慰剂。在495例随机分组时CMV DNA检测不到的患者中，莱特莫韦组中有临床意义的CMV感染或在移植后24周被插补为主要终点事件的患者少于安慰剂组（325例患者中的122例[37.5%] vs. 170例患者中的103例[60.6%]，P
BACKGROUNDCytomegalovirus (CMV) infection remains a common complication after allogeneic hematopoietic-cell transplantation. Letermovir is an antiviral drug that inhibits the CMV-terminase complex.METHODSIn this phase 3, double-blind trial, we randomly assigned CMV-seropositive transplant recipients, 18 years of age or older, in a 2:1 ratio to receive letermovir or placebo, administered orally or intravenously, through week 14 after transplantation; randomization was stratified according to trial site and CMV disease risk. Letermovir was administered at a dose of 480 mg per day (or 240 mg per day in patients taking cyclosporine). Patients in whom clinically significant CMV infection (CMV disease or CMV viremia leading to preemptive treatment) developed discontinued the trial regimen and received anti-CMV treatment. The primary end point was the proportion of patients, among patients without detectable CMV DNA at randomization, who had clinically significant CMV infection through week 24 after transplantation. Patients who discontinued the trial or had missing end-point data at week 24 were imputed as having a primary endpoint event. Patients were followed through week 48 after transplantation.RESULTSFrom June 2014 to March 2016, a total of 565 patients underwent randomization and received letermovir or placebo beginning a median of 9 days after transplantation. Among 495 patients with undetectable CMV DNA at randomization, fewer patients in the letermovir group than in the placebo group had clinically significant CMV infection or were imputed as having a primary end-point event by week 24 after transplantation (122 of 325 patients [37.5%] vs. 103 of 170 [60.6%], P