CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Invasive fungal infections after CD19 chimeric antigen receptor T-cell therapy for B-cell lymphoma: a Lymphoma study association study from the DESCAR-T (Dispositif d'Enregistrement et Suivi des patients traités par CAR-T cells) registry.
Invasive fungal infections after CD19 chimeric antigen receptor T-cell therapy for B-cell lymphoma: a Lymphoma study association study from the DESCAR-T (Dispositif d'Enregistrement et Suivi des patients traités par CAR-T cells) registry.
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尽管接受 CD19 CAR-T 细胞治疗的 B 细胞淋巴瘤患者中 IFI 发生率低,但感染相关死亡率高,凸显了对高危患者进行个体化预防和快速诊断的必要性。
描述法国DESCAR-T 国家登记中,B细胞恶性肿瘤患者接受嵌合抗原受体(CAR)T细胞疗法后侵袭性真菌感染(IFI)的情况,并评估该人群IFI相关危险因素。
开展多中心队列研究,描述接受CD19 CAR-T 细胞治疗的复发/难治性B细胞淋巴瘤成人患者的IFI情况。通过法国DESCAR-T 登记系统识别患者,回顾性收集临床和生物学数据,并根据欧洲癌症研究与治疗组织(EORTC)标准对IFI进行分类。
2018至2022年登记的1012例患者中,32例(3.1%)发生确诊(14例)、很可能(12例)或可能(6例)IFI。感染发生时间中位数为29.5天(四分位距16.5–79.5天)。最常见的霉菌感染为侵袭性曲霉病,32例中有11例;最常见的酵母菌感染为念珠菌血症,共12例。感染患者IFI相关死亡率为21.8%(32例中7例)。多因素分析识别出多项IFI相关危险因素:年龄较大、既往治疗线数较多、既往接受异基因造血细胞移植、接受抗白细胞介素-1受体拮抗剂治疗,以及IFI发生前有细菌感染。IFI患者总生存期中位数为6个月(95%置信区间1.0–20.6),未感染者为25.4个月(95%置信区间20.5–32.0)。IFI患者无进展生存期中位数为3.2个月(95%置信区间0.8–18.3),未感染者为5.8个月(95%置信区间4.5–6.7)。
尽管接受CD19 CAR-T 治疗的B细胞淋巴瘤患者IFI发生率较低,但其感染相关死亡率较高,凸显了对高危患者采取个体化预防和快速诊断的必要性。
To describe the landscape of invasive fungal infections (IFIs) after chimeric antigen receptor (CAR) T-cell therapy for B-cell malignancies from the French national DESCAR-T registry and evaluate risk factors associated with invasive fungal infections in this population.
We conducted a multicentre cohort study to describe the landscape of IFIs in adults with relapsed or refractory B-cell lymphoma treated with CD19 CAR T-cell therapy. Patients were identified through the French DESCAR-T registry. Clinical and biological data were collected retrospectively. Each IFI was classified according to the European Organization for Research and Treatment of Cancer (EORTC) criteria.
Among the 1012 patients included in the registry from 2018 to 2022, 32 patients (3.1%) presented with proven (n = 14/32), probable (n = 12/32), or possible (n = 6/32) IFIs. The median time to onset was 29.5 days (IQR 16.5-79.5 days). The most frequent mould infection was invasive aspergillosis, occurring in 11 of 32 patients, whereas the most frequent yeast infection was candidemia occurring in 12 of 32 patients. The IFI-related mortality rate among infected patients was 21.8% (7/32 patients). Multivariate analysis identified several risk factors associated with IFIs: advanced age, number of prior lines of therapy, prior allogeneic haematopoietic cell transplantation, antiinterleukin-1 receptor antagonist treatments, and pre-IFI bacterial infection. The median overall survival of patients with IFIs was 6 months (95% CI, 1.0-20.6) compared with 25.4 months (95% CI, 20.5-32.0) in the noninfected population. The median progression-free survival of patients with IFIs was 3.2 (95% CI, 0.8-18.3) months compared with 5.8 months (95% CI, 4.5-6.7) in the noninfected population.
Despite the low incidence of IFI in B-cell lymphoma patients treated with CD19 CAR T-cell therapy, the high infectious mortality underscore the need for individualized prophylaxis and rapid diagnosis for high-risk patients.
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