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:Cancer treatment-related cardiovascular toxicity according to the ESC definition in patients receiving CAR T-cell therapy.
Cancer treatment-related cardiovascular toxicity according to the ESC definition in patients receiving CAR T-cell therapy.
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尽管半数患者符合 ESC 关于 CTR-CVT 的标准,但 CAR-T 细胞治疗后具有临床相关性的心脏事件并不常见。这些发现提示,生物标志物升高可能导致过度分类,并强调在评估 CAR-T 细胞接受者的心脏毒性时重视临床相关性的重要性。
嵌合抗原受体(CAR)T细胞疗法显著改善了难治性血液系统恶性肿瘤的结局,但可能导致心血管并发症,尤其是在细胞因子释放综合征(CRS)的背景下。关于2022年ESC心脏肿瘤学指南所定义的癌症治疗相关心血管毒性(CTR-CVT)在CAR-T 细胞疗法背景下的发生率、严重程度及预后相关性的真实世界数据仍然有限。
这项回顾性单中心研究纳入104例于2019年9月至2024年2月期间因急性淋巴细胞白血病、非霍奇金淋巴瘤和多发性骨髓瘤接受CAR-T 细胞治疗的患者。主要终点为住院期间新发CTR-CVT,定义为癌症治疗相关心功能障碍(CTRCD)、心律失常、心肌梗死、心源性休克或心血管死亡。分析了临床特征、生物标志物、超声心动图参数、CRS/ICANS严重程度及生存结局。
52例患者(50%)符合CTR-CVT标准,主要由于无症状生物标志物升高。CTRCD发生于48.1%,而临床显著事件罕见:3例患者出现症状性CTRCD,1例发生心源性休克,未观察到心肌梗死或心血管死亡。心血管事件发生较早,并与更高级别的CRS和ICANS以及炎症标志物升高相关。基线左心室射血分数降低、收缩期肺动脉压升高、体能状态受损以及使用β受体阻滞剂与CTR-CVT风险增加相关。CTR-CVT患者的生存率在数值上较低,但未达到统计学显著性。
Chimeric antigen receptor (CAR) T-cell therapy has substantially improved outcomes in refractory hematologic malignancies but may cause cardiovascular complications, particularly in the context of cytokine release syndrome (CRS). Real-world data on incidence, severity, and prognostic relevance of cancer therapy-related cardiovascular toxicity (CTR-CVT) defined by the 2022 ESC cardio-oncology guidelines remain in the context of CAR-T cell therapy limited.
This retrospective single-center study includes 104 patients treated with CAR T-cells between 09/2019 and 02/2024 for acute lymphoblastic leukemia, non-Hodgkin lymphoma and multiple myeloma. The primary endpoint was new-onset CTR-CVT during hospital stay, defined as cancer therapy-related cardiac dysfunction (CTRCD), arrhythmia, myocardial infarction, cardiogenic shock, or cardiovascular death. Clinical characteristics, biomarkers, echocardiographic parameters, CRS/ICANS severity, and survival outcomes were analyzed.
Fifty-two patients (50%) met criteria for CTR-CVT, predominantly due to asymptomatic biomarker elevation. CTRCD occurred in 48.1%, whereas clinically significant events were rare: three patients developed symptomatic CTRCD, one experienced cardiogenic shock, and no myocardial infarctions or cardiovascular deaths were observed. Cardiovascular events occurred early and were associated with higher-grade CRS and ICANS, as well as elevated inflammatory markers. Reduced baseline left ventricular ejection fraction, elevated systolic pulmonary artery pressure, impaired performance status, and beta-blocker use were associated with increased CTR-CVT risk. Survival was numerically lower in patients with CTR-CVT but did not reach statistical significance.
Although half of patients fulfilled ESC criteria for CTR-CVT, clinically relevant cardiac events after CAR T-cell therapy were uncommon. These findings suggest potential overclassification driven by biomarker elevations and underscore the importance of emphasizing clinical relevance when assessing cardiotoxicity in CAR T-cell recipients.
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