决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Chimeric antigen receptor T-cell therapy and cardiovascular outcomes in US Medicare beneficiaries.
在接受 CAR-T 的最大规模全国性老年人群样本中,5.8% 的患者发生 MACE,且与院内死亡率和 1 年死亡率升高相关。
背景与目的:CAR-T 细胞疗法是一种细胞免疫疗法,可提高复发性血液系统恶性肿瘤患者的生存率。然而,其与主要不良心血管事件(MACE)的关联研究有限,尤其是在老年人群中。本研究调查了美国接受CAR-T治疗的老年患者发生MACE的情况、相关风险因素及其对生存的影响。 方法:纳入2018年至2023年接受住院CAR-T治疗、年龄超过65岁的Medicare按服务收费计划受益人。基线特征在CAR-T治疗前12个月内评估。MACE定义为以下事件的复合终点:急性心力衰竭(HF)、心源性休克、心肌梗死、心脏压塞、室性心律失常、完全性房室传导阻滞或卒中。多变量模型对人口学特征、恶性肿瘤类型及基线心血管合并症进行了调整。 结果:在3292例接受CAR-T治疗的患者中,191例(5.8%)发生MACE。最常见的事件是急性HF(3.1%),其次是缺血性卒中(1.3%)和出血性卒中(1%)。治疗前房颤/房扑[校正比值比(aOR)1.52(1.08-2.16)]、心肌病[aOR 2.49(1.75-3.54)]和脑血管疾病[aOR 2.40(1.30-4.43)]与MACE独立相关。在2021-23年,MACE还与免疫效应细胞相关神经毒性综合征及较高级别的细胞因子释放综合征相关。MACE与较高的院内死亡率[aOR 16.9(11.0-26.1)]及出院后1年死亡率[校正风险比1.91(1.46-2.49)]相关。 结论:在接受CAR-T治疗的老年人群中规模最大的全国性样本中,5.8%的患者发生MACE,且MACE与院内及1年死亡率升高相关。仍需进一步研究预防和减轻相关事件的措施。
BACKGROUND AND AIMS: Chimeric antigen receptor T-cell (CAR-T) therapies are cellular immunotherapies that improve survival in patients with relapsed haematologic malignancies. However, their association with major adverse cardiovascular events (MACE) has received limited study, particularly in older adults. This study investigated the incidence of MACE, associated risk factors, and their impact on survival among older patients undergoing CAR-T in the USA. METHODS: Medicare fee-for-service beneficiaries over 65 who received inpatient CAR-T therapy between 2018 and 2023 were included. Baseline characteristics were assessed during the 12 months preceding CAR-T. MACE were defined as a composite of acute heart failure (HF), cardiogenic shock, myocardial infarction, cardiac tamponade, ventricular arrhythmia, complete heart block, or stroke. Multivariable models were adjusted for demographics, malignancy type, and baseline cardiovascular comorbidities. RESULTS: Among 3292 patients receiving CAR-T, 191 (5.8%) had MACE. Most common events were acute HF (3.1%), followed by ischaemic (1.3%) and haemorrhagic stroke (1%). Pre-treatment atrial fibrillation/flutter [adjusted odds ratio (aOR) 1.52 (1.08-2.16)], cardiomyopathy [aOR 2.49 (1.75-3.54)], and cerebrovascular disease [aOR 2.40 (1.30-4.43)] were independently associated with MACE. In 2021-23, MACE were also associated with immune effector cell-associated neurotoxicity syndrome and higher-grade cytokine release syndrome. MACE were associated with higher in-hospital mortality [aOR 16.9 (11.0-26.1)] and 1-year mortality after discharge [adjusted hazard ratio 1.91 (1.46-2.49)]. CONCLUSIONS: In the largest national sample of older adults receiving CAR-T, MACE occurred in 5.8% of patients and were associated with increased in-hospital and 1-year mortality. Further investigation into preventive and mitigating measures is needed.
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