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.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Cardiovascular events in patients treated with chimeric antigen receptor T-cell therapy for aggressive B-cell lymphoma.
Cardiovascular events in patients treated with chimeric antigen receptor T-cell therapy for aggressive B-cell lymphoma.
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标准治疗(SOC)嵌合抗原受体(CAR)T细胞疗法,如axicabtagene ciloleucel(axi-cel)和tisagenlecleucel(tisa-cel),与多系统毒性相关。关于与SOC axi-cel或tisa-cel相关的心血管(CV)事件,目前可获取的信息有限。在导致其获得美国食品药品监督管理局批准的临床试验中,伴有CV合并症、器官功能障碍或体能状态较差的患者通常被排除在外。更好地了解真实世界环境中的CV毒性,将有助于为接受这些细胞疗法的患者的治疗选择和管理提供更好的依据。
在此,我们回顾性分析了接受SOC axi-cel或tisa-cel治疗的复发/难治性大B细胞淋巴瘤成年患者的特征和结局。在评估的165例患者中,27例(16%)发生了至少1次30天(30-d)主要不良心血管事件(MACE)。累计来看,这些患者发生了21例心律失常、4例心力衰竭/心肌病加重、4例脑血管意外、3例心肌梗死,另有1例患者死于心肌梗死。与30-d MACE风险增加显著相关的因素包括年龄60岁、细胞因子释放综合征(CRS)发生更早、CRS 3级、CRS持续时间长以及使用tocilizumab。在中位随访时间16.2个月(范围,14.3-19.1)后,30-d MACE的发生与无进展生存期或总生存期均无显著相关性。
我们的结果提示,30-d MACE的发生在老年、伴有早期、严重且持续时间较长的CRS的患者中更为常见。然而,由于随访时间有限,仍需更大规模的前瞻性研究,并建议对这些患者进行多学科管理。
Standard of care (SOC) chimeric antigen receptor (CAR) T-cell therapies such as axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are associated with multisystem toxicities. There is limited information available about cardiovascular (CV) events associated with SOC axi-cel or tisa-cel.
Patients with CV comorbidities, organ dysfunction, or lower performance status were often excluded in the clinical trials leading to their Food and Drug Adminsitration approval. An improved understanding of CV toxicities in the real-world setting will better inform therapy selection and management of patients receiving these cellular therapies.
Here, we retrospectively reviewed the characteristics and outcomes of adult patients with relapsed/refractory large B-cell lymphoma treated with SOC axi-cel or tisa-cel. Among the 165 patients evaluated, 27 (16%) developed at least one 30-day (30-d) major adverse CV event (MACE). Cumulatively, these patients experienced 21 arrhythmias, four exacerbations of heart failure/cardiomyopathy, four cerebrovascular accidents, three myocardial infarctions, and one patient died due to myocardial infaction.
Factors significantly associated with an increased risk of 30-d MACE included age 60 years, an earlier start of cytokine release syndrome (CRS), CRS grade 3, long duration of CRS, and use of tocilizumab. After a median follow-up time of 16. 2 months (range, 14. 3-19. 1), the occurrence of 30-d MACE was not significantly associated with progression-free survival or with overall survival.
Our results suggest that the occurrence of 30-d MACE is more frequent among patients who are elderly, with early, severe, and prolonged CRS.
However, with limited follow-up, larger prospective studies are needed, and multidisciplinary management of these patients is recommended.
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