BACKGROUND Isavuconazole is a broad-spectrum triazole approved for treatment of invasive fungal infections (IFI). We evaluated isavuconazole for antifungal prophylaxis after allogeneic hematopoietic cell transplant (HCT). MATERIALS AND METHODS In this open-label, single-arm study, adult patients admitted for first HCT received micafungin 150 mg intravenously (IV) daily from admission through day+7 post-transplant (D+7) (+/- 2 days) followed by isavuconazole prophylaxis (IV/PO 372 mg q8 hours for 6 doses and then 372 mg daily) through maximum D+98 post-HCT. Patients were followed through D+182. The primary endpoint was prophylaxis failure defined as discontinuation of prophylaxis for proven/probable IFI; systemic antifungal therapy for >14 days for suspected IFI; toxicity leading to discontinuation; or adverse event (AE). RESULTS From June 2017 through October 2018, 99 patients were enrolled in the study and 95 patients were included in the analyses. The median age was 57 years (interquartile range [IQR], 50-66). Sixty-four (67%) patients received peripheral blood, 17(18%) marrow, and 14 (15%) cord blood allograft for acute leukemia (55%), lymphoma (17%), myelodysplastic syndrome (16%), or other hematologic diseases (14%). A third (31, 33%) of patients received CD34+ selected HCT. Isavuconazole prophylaxis was given for a median of 90 days (IQR, 87-91). Ten (10.7%) patients met the primary endpoint. Candidemia occurred in 3 (3.1%) patients, one of whom had grade 3 skin graft-versus-host disease (GVHD). Toxicity leading to discontinuation occurred in 7 (7.4%) patients. The most common toxicity was liver function abnormalities in five patients, including grade 1 transaminitis in two patients and grade 3 hyperbilirubinemia in three patients. Four patients (4.2%) had early discontinuation of isavuconazole for reasons not meeting primary endpoint. Six patients died during the study; three during prophylaxis and 3 during follow up. No death was attributed to isavuconazole. CONCLUSIONS 85% allogeneic HCT recipients completed isavuconazole prophylaxis per protocol. The rate of breakthrough candidemia was 3.1% and there were no invasive mold infections. Our data support the utility of isavuconazole for antifungal prophylaxis after HCT.

中文翻译：

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艾伐康唑预防异基因造血细胞移植患者侵袭性真菌感染的单中心，开放标签试验。

背景技术Isavuconazole是一种广谱三唑，被批准用于治疗侵袭性真菌感染（IFI）。在异基因造血细胞移植（HCT）后，我们评估了伊沙康康唑对真菌的预防作用。材料与方法在这项开放性单臂研究中，首次入院的成年患者从入院至移植后第7天（D + 7）每天静脉内（IV）接受米卡芬净150 mg（+/- 2天）然后在HCT后最大D + 98期间预防艾沙康康唑（IV / PO 372 mg，每8小时一次，共6剂，然后每天372 mg）。通过D + 182对患者进行随访。主要终点为预防失败，定义为已证实/可能的IFI停止预防。怀疑有IFI的系统性抗真菌治疗时间超过14天；毒性导致停药；或不良事件（AE）。结果2017年6月至2018年10月，该研究招募了99位患者，分析中纳入了95位患者。中位年龄为57岁（四分位间距[IQR]，50-66岁）。急性白血病（55％），淋巴瘤（17％），骨髓增生异常综合症（16％）接受了64位（67％）患者的外周血，17％（18％）的骨髓和14位（15％）的脐血移植其他血液学疾病（14％）。三分之一（31，33％）的患者接受了CD34 +选择的HCT。预防Isavuconazole的中位数为90天（IQR，87-91）。十名患者（10.7％）达到了主要终点。3例患者（3.1％）发生了念珠菌血症，其中1例患有3级皮肤移植物抗宿主病（GVHD）。有7名（7.4％）患者发生了导致停药的毒性反应。最常见的毒性反应是五位患者的肝功能异常，包括两名患者的1级转氨性炎和三名患者的3级高胆红素血症。四名患者（4.2％）由于未达到主要终点的原因而早期停用了艾沙康康唑。研究期间有6名患者死亡；预防期间3例，随访期间3例。没有死亡归因于伊沙康康唑。结论：根据方案，异源HCT接受者中有85％完成了艾伐康唑预防。突破性念珠菌血症的发生率为3.1％，没有侵袭性霉菌感染。我们的数据支持伊沙康康唑用于HCT后预防真菌的效用。预防期间3例，随访期间3例。没有死亡归因于伊沙康康唑。结论：根据协议，异源HCT接受者中有85％完成了艾伐康唑预防。突破性念珠菌血症的发生率为3.1％，没有侵袭性霉菌感染。我们的数据支持伊沙康康唑用于HCT后预防真菌的效用。预防期间3例，随访期间3例。没有死亡归因于伊沙康康唑。结论：根据方案，异源HCT接受者中有85％完成了艾伐康唑预防。突破性念珠菌血症的发生率为3.1％，没有侵袭性霉菌感染。我们的数据支持伊沙康康唑用于HCT后预防真菌的效用。