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:Cardiac adverse events after Chimeric Antigen Receptor (CAR) T cell therapies: an updated systematic review and meta-analysis.
Cardiac adverse events after Chimeric Antigen Receptor (CAR) T cell therapies: an updated systematic review and meta-analysis.
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CAR-T 细胞治疗常导致心脏毒性,由细胞因子释放综合征介导。警惕性监测和个体化治疗对于减轻这些效应至关重要。重要的是,各组间心脏死亡率无显著差异,这为优化预防性干预和降低 CAR-T 细胞治疗后风险提供了见解。
嵌合抗原受体(CAR)T细胞疗法是治疗难治性或复发性血液系统恶性肿瘤的一种新的革命性方法,CAR-T 细胞疗法与细胞因子释放综合征(CRS)和心脏毒性相关。我们进行了一项系统综述和meta分析,以确定CAR-T 细胞疗法中心血管事件(CVE)的发生率和预测因素。
我们检索了PubMed、Embase、Cochrane Library和ClinicalTrials.gov,以寻找报告CAR-T 细胞接受者心血管结局的研究。研究方案已列入国际前瞻性系统评价注册库(PROSPERO ID:CRD42023478602)。本研究共纳入23项研究。
CVE的合并发生率分别为:心律失常54%、心力衰竭30%、心肌病20%、急性冠脉综合征10%、心脏骤停7%。发生CVE的患者中,细胞因子释放综合征2级的发生率更高(RR 2.36,95% CI 1.86-2.99)。在我们的meta分析中,心脏死亡率的发生率为2%(95% CI:1%-3%)。CVE组的左心室射血分数下降幅度更大(-9.4% 对 -1.5%,p < 0.001)。BNP、CRP、肌酐和铁蛋白等心脏生物标志物也升高。
Chimeric antigen receptor (CAR) T-cell therapy is a new revolutionary method for treating refractory or relapsed hematologic malignancies, CAR T-cell therapy has been associated with cytokine release syndrome (CRS) and cardiotoxicity. We directed a systematic review and meta-analysis to determine the incidence and predictors of cardiovascular events (CVE) with CAR T-cell therapy.
We investigated PubMed, Embase, Cochrane Library, and ClinicalTrials.gov for studies reporting cardiovascular outcomes in CAR-T cell recipients. The study protocol was listed in the International Prospective Register of Systematic Reviews (PROSPERO ID: CRD42023478602). Twenty-three studies were included in this study.
The pooled incidence of CVE was 54% for arrhythmias, 30% for heart failure, 20% for cardiomyopathy, 10% for acute coronary syndrome, and 7% for cardiac arrest. Patients with CVE had a higher incidence of cytokine release syndrome grade 2 (RR 2.36, 95% CI 1.86-2.99). The incidence of cardiac mortality in our meta-analysis was 2% (95% CI: 1%-3%). Left ventricular ejection fraction decline was greater in the CVE group (-9.4% versus -1.5%, p < 0.001). Cardiac biomarkers like BNP, CRP, creatinine, and ferritin were also elevated.
CAR T-cell therapy commonly leads to cardiotoxicity, mediated by cytokine release syndrome. Vigilant monitoring and tailored treatments are crucial to mitigate these effects. Importantly, there's no significant difference in cardiac mortality between groups, suggesting insights for optimizing preventive interventions and reducing risks after CAR T-cell therapy.
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