■评估心血管风险对癌症患者至关重要。先前的回顾性研究表明,CART细胞疗法具有潜在的心脏毒性。我们旨在前瞻性评估心脏毒性以及心脏生物标志物和经典危险因素的预测价值(年龄,心功能,糖尿病,动脉高血压,吸烟)用于心脏事件和全因死亡率(ACM)。
■在这项前瞻性队列研究中,所有接受CART细胞构建体治疗的患者(axi-cel,tisa-cel,Brexu-cel,ide-cel,包括2018年10月1日至2022年9月30日在海德堡大学医院的第三代CARHD-CAR-1)。监测包括用生物标志物进行心脏评估(高敏肌钙蛋白T(hs-cTnT),N末端脑钠肽(NT-proBNP),12导联心电图,和二维超声心动图。ACM被定义为主要研究终点,而心脏毒性,由心力衰竭或射血分数下降的临床综合征定义,作为次要终点。
■总的来说,137名患者(中位年龄60,范围20-83,IQR16),包括在研究中。46例患者在随访期间死亡(中位数0.75年,范围0.02-4.33,IQR0.89)57个月,中位生存期为0.57年(范围为0.03-2.38年,IQR0.79)。中隔壁厚度超过11mm(HR2.48,95%-CI=1.10-5.67,p=0.029)与ACM风险增加相关,观察到治疗前左心室射血分数降低的趋势(LVEF<40%;HR9.17,95%-CI=1.30-183.11,p=0.051)。93名患者达到了次要终点,而没有基线参数能够预测风险升高。然而,在CAR输注后的前14天内,hs-cTnT从基线的50%或更高的变化预测了ACM(HR3.81,95%-CI=1.58-9.45;p=0.003)。没有基线特征能够预测心脏事件的发生率。
■降低的淋巴清除前射血分数和早期输注后生物标志物动力学可能与增加的ACM和心脏毒性事件有关。这些发现可能有助于识别可能从强化心血管肿瘤监测中受益的患者。
■德国心血管研究中心,德国研究基金会,联邦教育和研究部。
UNASSIGNED: Assessment of cardiovascular risk is critical for patients with cancer. Previous retrospective studies suggest potential cardiotoxicity of CAR T cell therapies. We aimed to prospectively assess cardiotoxicity and the predictive value of cardiac biomarkers and classical risk factors (age, cardiac function, diabetes, arterial hypertension, smoking) for cardiac events and all-cause mortality (ACM).
UNASSIGNED: In this prospective cohort study, all patients treated with CAR T cell constructs (axi-cel, tisa-cel, brexu-cel, ide-cel, or the 3rd generation CAR HD-CAR-1) from Oct 1, 2018, to Sept 30, 2022 at the University Hospital Heidelberg were included. Surveillance included cardiac assessment with biomarkers (high-sensitive Troponin T (hs-cTnT), N-terminal brain natriuretic peptide (NT-proBNP)), 12-lead-ECG, and 2D echocardiography. ACM was defined as the primary study endpoint, while cardiotoxicity, defined by clinical syndromes of heart failure or decline in ejection fraction, served as a secondary endpoint.
UNASSIGNED: Overall, 137 patients (median age 60, range 20-83, IQR 16), were included in the study. 46 patients died during the follow up period (median 0.75 years, range 0.02-4.33, IQR 0.89) 57 month, with a median survival of 0.57 years (range 0.03-2.38 years, IQR 0.79). A septal wall thickness above 11 mm (HR 2.48, 95%-CI = 1.10-5.67, p = 0.029) was associated with an increased risk of ACM, with a trend seen for reduced left ventricular ejection fraction prior to therapy (LVEF <40%; HR 9.17, 95%-CI = 1.30-183.11, p = 0.051). Secondary endpoint was reached by 93 patients while no baseline parameter was able to predict an elevated risk. However, hs-cTnT change from baseline of 50% or more during the first 14 days after CAR infusion predicted ACM (HR 3.81, 95%-CI = 1.58-9.45; p = 0.003). None of the baseline characteristics was able to predict the incidence of cardiac events.
UNASSIGNED: Reduced pre-lymphodepletion ejection fraction and early post-infusion biomarker kinetics may be associated with increased ACM and cardiotoxicity events. These findings may help to identify patients who could benefit from intensified cardio-oncological surveillance.
UNASSIGNED: The German Center for Cardiovascular Research, German Research Foundation, and the Federal Ministry of Education and Research.