Invasive fungal infections in acute myeloid leukemia treated with venetoclax and hypomethylating agents
Invasive fungal infections in acute myeloid leukemia treated with venetoclax and hypomethylating agents
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DOI：
10.1182/bloodadvances.2019000930
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发表时间：
2019-12-10
期刊：
影响因子：
7.5
通讯作者：
Pullarkat, Vinod
中科院分区：
文献类型：
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作者：
Aldoss, Ibrahim;Dadwal, Sanjeet;Pullarkat, Vinod
维奈托克与低甲基化药物（VEN-HMAs）联合治疗在新诊断和复发/难治性（r/r）急性髓性白血病（AML）中显示出有希望的活性。VEN-HMA治疗导致血细胞减少延长，从而使患者暴露于侵袭性真菌感染（IFIs）。在这里，我们回顾性研究了一组119例接受VEN-HMAs治疗的AML患者，并分析了IFIs的发生率以及我们的抗真菌预防措施，旨在确定IFIs的性质和风险因素及其与所用抗真菌预防措施类型的相关性。38%的患者预期的抗真菌预防性治疗为米卡芬净，41%的患者为唑类，21%的患者为无。年龄较大与无抗真菌预防或米卡芬净使用以及唑类药物使用较少相关（P = 0.043）。我们记录了15例（12.6%）患者发生了可能或证实的IFIs，开始治疗后中位发病时间为72天（范围35-281）。与VEN-HMA治疗的应答者相比，无应答者中IFIs更常见（22% vs 6%，P = 0.0132），与新诊断的AML相比，r/r（19%对5%，P = .0498）;然而，所用的抗真菌预防、患者年龄、低甲基化剂时间表、既往同种异体移植史初始中性粒细胞减少持续时间不影响治疗期间IFIs的发展。我们的结论是，在VEN-HMA治疗期间，IFIs的总体风险较低。无应答者和在r/r环境中接受治疗的患者发生IFIs的风险较高;这些患者需要重新评估其抗真菌预防措施，以最大限度地降低治疗期间发生IFIs的风险。
The combination of venetoclax with hypomethylating agents (VEN-HMAs) showed promising activity in newly diagnosed and relapsed/refractory (r/r) acute myeloid leukemia (AML). Treatment with VEN-HMAs results in prolonged cytopenia, thereby exposing patients to invasive fungal infections (IFIs). Here, we retrospectively studied a cohort of 119 AML patients treated with VEN-HMAs and analyzed the occurrence of IFIs, as well as our practice of antifungal prophylaxis, with the aim to identify the nature and risk factors for IFIs and their association with the type of antifungal prophylaxis used. The intended antifungal prophylaxis was micafungin in 38% of patients, azoles in 41% of patients, and none in 21% of patients. Older age was associated with no antifungal prophylaxis or micafungin use and lesser use of azoles (P = .043). We recorded 15 (12.6%) patients who developed probable or proven IFIs, with a median onset of 72 days (range, 35-281) after starting therapy. IFIs were more common among nonresponders compared with responders to VEN-HMA therapy (22% vs 6%, P = .0132) and in r/r compared with newly diagnosed AML (19% vs 5%, P = .0498); however, the antifungal prophylaxis used, patient age, hypomethylating agent schedule, history of prior allogeneic transplant, and initial neutropenia duration did not influence the development of IFIs during therapy. We conclude that the overall risk of IFIs during VEN-HMA therapy is low. The risk of IFIs is higher in nonresponders and in those who were treated in the r/r setting; these patients need reevaluation of their antifungal prophylaxis to minimize the risk of IFIs during therapy.