Background

There are limited real-life data on isavuconazole prophylaxis and treatment of invasive mold infections (IMI) in hematological patients and allogeneic hematopoietic cell transplant (HCT) recipients.

Objectives

Primary objective was to describe the indications of real-life isavuconazole administration at a university hospital. Secondary objectives included the description of liver function tests and QTc interval between baseline and end of treatment (EOT), clinical outcomes and breakthrough IMI by the EOT.

Patients/Methods

This was a 5-year single-center retrospective study of all adult patients with acute myeloid leukemia and/or allogeneic HCT recipients who received isavuconazole as prophylaxis and/or treatment between June 1, 2016, and July 31, 2020.

Results

Among 30 identified patients, the indications for isavuconazole administration were adverse events associated with prior antifungal treatment (N: 18, 60%: hepatotoxicity, renal insufficiency, long QTc interval, neurotoxicity, and potential drug–drug interactions in 6, 4, 3, 1 and 4 patients, respectively), clinical efficacy (N: 5, 16.6%), and other reasons (N: 10, 33.3%; 5/10 patients treated with isavuconazole to facilitate hospital discharge with orally administered appropriate treatment). Alanine aminotransferase significantly decreased from baseline (mean: 129 IU/L, range: 73, 202) to a mean of 48 IU/L (range: 20, 80) by day 14 (P-value: 0.02), 23.5 IU/L (range: 20, 27) by day 28 (P-value: 0.03) and 16.5 IU/L (range: 16, 17) by day 42 (P-value: 0.009). The QTc interval decreased from baseline (mean: 456.8 ms, range: 390, 533) to EOT (mean: 433.8 ms, range: 400, 472; P-value: 0.03). The mean isavuconazole plasma concentration was 2.9 mg/L (range: 0.9, 6.7). There was no breakthrough IMI observed.

Conclusion

Isavuconazole is a safe and reliable antifungal agent in complex hematological patients, with relatively low hepatotoxicity and QTc interval shortening properties.

中文翻译：

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艾沙康唑用于高危血液病患者的临床考虑：单中心 5 年经验

背景

关于艾沙康唑预防和治疗血液病患者和异基因造血细胞移植 (HCT) 受者的侵袭性霉菌感染 (IMI) 的真实数据有限。

目标

主要目的是描述在大学医院实际使用艾沙康唑的适应症。次要目标包括描述肝功能测试和基线和治疗结束 (EOT) 之间的 QTc 间隔、临床结果和 EOT 的突破性 IMI。

患者/方法

这是一项为期 5 年的单中心回顾性研究，对象为 2016 年 6 月 1 日至 2020 年 7 月 31 日期间接受艾沙康唑作为预防和/或治疗的所有成人急性髓性白血病和/或异基因 HCT 接受者。

结果

在 30 名已确定的患者中，艾沙康唑给药的适应症是与先前抗真菌治疗相关的不良事件（N：18，60%：肝毒性、肾功能不全、QTc 间期长、神经毒性和潜在的药物-药物相互作用 6、4、3、分别为 1 例和 4 例患者）、临床疗效（N：5, 16.6%）和其他原因（N : 10, 33.3%；5/10 患者使用艾沙康唑以方便出院并口服适当治疗）。到第 14 天，丙氨酸氨基转移酶从基线（平均值：129 IU/L，范围：73, 202）显着降低至平均值 48 IU/L（范围：20, 80）（P值：0.02），23.5 IU/L （范围：20、27）到第 28 天（P-值：0.03）和 16.5 IU/L（范围：16、17）到第 42 天（P -值：0.009）。QTc 间期从基线（平均值：456.8 ms，范围：390、533）降低到 EOT（平均值：433.8 ms，范围：400、472；P值：0.03）。艾沙康唑的平均血浆浓度为 2.9 mg/L（范围：0.9、6.7）。没有观察到突破性IMI。

结论

艾沙康唑是一种对复杂血液病患者安全可靠的抗真菌药物，具有相对较低的肝毒性和缩短 QTc 间期的特性。