Sassine Joseph, Agudelo Higuita Nelson Iván, Siegrist Emily A, Saeedi Arman, Corbisiero Michaele Francesco, Connelly Patrick, Bastias Alfonso G, Dib Rita Wilson, Henao-Cordero José, Chastain Daniel B, Chiu Chia-Yu, Henao-Martínez Andrés F
Infectious Diseases Section, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Infectious Diseases Section, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Instituto de Enfermedades Infecciosas y Parasitología Antonio Vidal, Tegucigalpa, Honduras.
Clin Microbiol Infect. 2025 Mar;31(3):466-472. doi: 10.1016/j.cmi.2024.11.008. Epub 2024 Nov 9.
This large database analysis aims to describe the incidence, timeline, and risk factors for viral and fungal infections after chimeric antigen receptor (CAR) T-cell therapy.
We queried a global research network database, TriNetX, for patients who received CAR T-cell therapy, who were identified and followed for the development of viral and fungal infections. Baseline demographic, oncologic history, laboratory data and medication histories were collected. We evaluated risk factors for respiratory viral infections (RVIs), herpesvirus, fungal infections and mortality using Cox regression.
A total of 2256 patients who received CAR T-cell therapy were included, 1867 (82.7%) were CD19-targeted and 400 (17.7%) were B-cell maturation antigen-targeted. After CAR T-cell infusion, RVIs were the most prevalent (23.3%) with a median onset of 160 days (interquartile range [IQR]: 52-348 days), whereas herpesvirus and fungal infections were less frequent, occurring in 13.6% and 11.4% of cases with median onsets of 71 (IQR, 18-252) and 73 days (IQR, 14-236 days), respectively. On multivariable Cox regression, independent predictors of RVI included acute lymphoblastic leukaemia (hazard ratio [HR], 1.61), prior haematopoietic cell transplant (HCT; HR, 1.29), cytokine release syndrome (HR, 1.41), hemophagocytic lymphohistiocytosis (HR, 1.96) and glucocorticoids (HR, 3.37). Prior HCT (HR, 2.00), hypogammaglobulinemia (HR, 1.51), immune effector cell-associated neurotoxicity syndrome (HR, 1.52) and hemophagocytic lymphohistiocytosis (HR, 1.99) were associated with a higher risk of herpesviruses. Independent predictors of fungal infections included prior HCT (HR, 1.59), cytokine release syndrome (HR, 1.58) and hypogammaglobulinemia (HR, 1.40). Idecabtagene vicleucel was associated with a lower risk of herpesvirus and fungal infections (HR, 0.39 and 0.44, respectively).
In a large cohort of CAR T-cell therapy recipients, RVIs were the most common but occurred later, whereas herpesvirus and fungal infections were less frequent but occurred earlier. Prospective studies investigating prophylaxis and pre-emptive monitoring strategies are needed in this population.
这项大型数据库分析旨在描述嵌合抗原受体（CAR）T细胞治疗后病毒和真菌感染的发生率、时间线及风险因素。
我们在全球研究网络数据库TriNetX中查询接受CAR T细胞治疗的患者，对其进行识别并跟踪病毒和真菌感染的发生情况。收集基线人口统计学、肿瘤病史、实验室数据及用药史。我们使用Cox回归评估呼吸道病毒感染（RVI）、疱疹病毒、真菌感染及死亡的风险因素。
共纳入2256例接受CAR T细胞治疗的患者，其中1867例（82.7%）以CD19为靶点，400例（17.7%）以B细胞成熟抗原为靶点。CAR T细胞输注后，RVI最为常见（23.3%），中位发病时间为160天（四分位间距[IQR]：52 - 348天），而疱疹病毒和真菌感染较少见，分别发生在13.6%和11.4%的病例中，中位发病时间分别为71天（IQR，18 - 252）和73天（IQR，14 - 236天）。在多变量Cox回归分析中，RVI的独立预测因素包括急性淋巴细胞白血病（风险比[HR]，1.61）、既往造血细胞移植（HCT；HR，1.29）、细胞因子释放综合征（HR，1.41）、噬血细胞性淋巴组织细胞增生症（HR，1.96）和糖皮质激素（HR，3.37）。既往HCT（HR，2.00）、低丙种球蛋白血症（HR，1.51）、免疫效应细胞相关神经毒性综合征（HR，1.52）和噬血细胞性淋巴组织细胞增生症（HR，1.99）与疱疹病毒感染风险较高相关。真菌感染的独立预测因素包括既往HCT（HR，1.59）、细胞因子释放综合征（HR，1.58）和低丙种球蛋白血症（HR，1.40）。idecabtagene vicleucel与疱疹病毒和真菌感染风险较低相关（HR分别为0.39和0.44）。
在一大群接受CAR T细胞治疗的患者中，RVI最常见但发病较晚，而疱疹病毒和真菌感染较少见但发病较早。该人群需要开展前瞻性研究以调查预防和抢先监测策略。
