Gibert Charles, Blaize Marion, Fekkar Arnaud
Institute of Microbiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; Université Claude Bernard Lyon 1, Villeurbanne, France.
Sorbonne Université, Centre d'Immunologie et des Maladies Infectieuses (CIMI)-Paris, Assistance Publique - Hôpitaux de Paris (AP-HP), Service de Parasitologie-Mycologie, Hopital de La Pitie-Salpetriere, Paris, France.
Clin Microbiol Infect. 2025 May;31(5):731-739. doi: 10.1016/j.cmi.2024.12.032. Epub 2024 Dec 30.
The Bruton tyrosine kinase inhibitor (BTKi) has emerged as a key treatment for B-cell lymphomas. Despite its efficacy in the treatment of malignancies, numerous cases of invasive fungal infections (IFI) have been reported in patients receiving ibrutinib, a first-generation BTKi. Cases of invasive aspergillosis have also been reported with acalabrutinib and zanubrutinib.
The objective of this study was to provide an overview of the pathogens involved, the time of onset of infections and factors influencing survival.
Data sources: PubMed, Embase and Web of Science databases were used, and the results were reported according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.
Case reports, case series, clinical trials and cohort studies were included.
All reported cases of IFI in patients treated with BTKi were analysed. For case reports/case series, demographic, microbiological and outcome data were retrieved. Assessment of risk of bias: Given the significant heterogeneity in clinical trials/cohort studies, only epidemiological analysis was performed, without formal incidence analysis. Methods of data synthesis: Epidemiologic data were presented as descriptive statistics.
In total, 25 215 patients from 92 retrospective and prospective clinical trials/cohort studies and 211 patients from 115 case reports/case series were included. Among clinical trials/cohorts, 736 IFI were reported, including 234 candidiasis (31.8%), 227 aspergillosis (30.8%) and 124 Pneumocystis jirovecii pneumonia (PJP) (16.8%). Among the case reports/case series, 155 (73.5%) had chronic lymphocytic leukaemia, and 56 (26.5%) had other malignancies. The main IFI were aspergillosis (n = 107, 50.7%), cryptococcosis (n = 33, 15.6%), PJP (n = 26, 12.3%) and mucormycosis (n = 23, 10.9%). The median delay between the initiation of BTKi and IFI was 2.3, 4.0, 3.0 and 3.0 for aspergillosis, cryptococcosis, PJP and mucormycosis, respectively. The survival rate improved when BTKi was discontinued during infection.
Targeted therapies in lymphocytic malignancies raised new issues concerning infectious complications. Monitoring IFI in patients receiving second- and third-generation BTKi is crucial for improving the management of these manifestations.
布鲁顿酪氨酸激酶抑制剂（BTKi）已成为B细胞淋巴瘤的关键治疗药物。尽管其在治疗恶性肿瘤方面疗效显著，但接受第一代BTKi伊布替尼治疗的患者中已报告了大量侵袭性真菌感染（IFI）病例。使用阿卡替尼和泽布替尼治疗时也报告了侵袭性曲霉病病例。
本研究的目的是概述所涉及的病原体、感染的发病时间以及影响生存的因素。
数据来源：使用了PubMed、Embase和Web of Science数据库，并根据系统评价和Meta分析的首选报告项目指南报告结果。
纳入病例报告、病例系列、临床试验和队列研究。
分析了所有报告的接受BTKi治疗患者的IFI病例。对于病例报告/病例系列，检索了人口统计学、微生物学和结局数据。偏倚风险评估：鉴于临床试验/队列研究存在显著异质性，仅进行了流行病学分析，未进行正式的发病率分析。数据合成方法：流行病学数据以描述性统计呈现。
总共纳入了92项回顾性和前瞻性临床试验/队列研究中的25215例患者以及115例病例报告/病例系列中的211例患者。在临床试验/队列中，报告了736例IFI，包括234例念珠菌病（31.8%）、227例曲霉病（30.8%）和124例耶氏肺孢子菌肺炎（PJP）（16.8%）。在病例报告/病例系列中，155例（73.5%）患有慢性淋巴细胞白血病，56例（26.5%）患有其他恶性肿瘤。主要的IFI为曲霉病（n = 107，50.7%）、隐球菌病（n = 33，15.6%）、PJP（n = 26，12.3%）和毛霉病（n = 23，10.9%）。侵袭性曲霉病、隐球菌病、PJP和毛霉病在开始使用BTKi至发生IFI的中位延迟时间分别为2.3、4.0、3.0和3.0。在感染期间停用BTKi时生存率有所提高。
淋巴细胞恶性肿瘤的靶向治疗引发了有关感染并发症的新问题。监测接受第二代和第三代BTKi治疗患者的IFI对于改善这些表现的管理至关重要。
