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:Predictive Factors and Baseline Risk Stratification for CAR-T Cell Therapy-Related Cardiovascular Toxicity.
Predictive Factors and Baseline Risk Stratification for CAR-T Cell Therapy-Related Cardiovascular Toxicity.
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7 种基线 CV 状况与 CAR-T 细胞相关 CVAE 显著相关。
接受潜在心脏毒性抗癌治疗患者的基线心血管(CV)风险分层至关重要。CAR-T 细胞疗法是治疗血液系统恶性肿瘤的突破性方法,但伴有不可忽视的心血管不良事件(CVAE)风险。本研究旨在识别CAR-T 相关CVAE预测因素,并开发相应风险分层评分。
对比发生与未发生CAR-T 相关CVAE患者的基线临床指标、生物标志物、超声心动图结果及药物治疗,开展荟萃分析。随后利用显著预测因素的合并相对危险度(RR)构建风险分层评分。
共纳入12项相关研究,涉及1,354例血液系统恶性肿瘤患者,多数接受CD19靶向CAR-T 治疗,其中228例(16.8%)发生CVAE。显著预测因素包括冠状动脉疾病[RR=2.27(95% CI 1.46–3.51)]、高脂血症[1.57(1.14–2.15)]、糖尿病[1.59(1.13–2.24)]、高血压[1.45(1.18–1.77)]、房颤[2.42(1.51–3.88)]、心力衰竭[2.74(1.62–4.61)]及吸烟[1.40(1.10–1.79)]。基于上述七项因素制定的风险评分命名为CART-7,范围0–33分;0–8分为低危,9–17分为中危,18–25分为高危,26–33分为极高危。
七种基线心血管疾病或危险因素与CAR-T 相关CVAE显著相关。仍需进一步验证CART-7评分,以支持其临床应用及CAR-T 治疗患者的基线心血管风险分层。
We conducted a meta-analysis of studies comparing baseline clinical, biomarker, echocardiographic findings, and pharmaceutical treatments between patients who developed CAR-T cell-related CVAE and those who did not. We subsequently used the pooled relative risks (RR) of significant predictors to construct a risk stratification score.
We identified 12 relevant studies encompassing a total of 1354 patients with haematologic malignancies, the majority of which were treated with CD19-directed CAR-T cell therapy, of whom 228 (16.8%) developed CVAE. Significant predictors of CAR-T cell-related CVAE included coronary artery disease [RR = 2.27 (95% confidence interval, 1.46-3.51)], hyperlipidaemia [1.57 (1.14-2.15)], diabetes [1.59 (1.13-2.24)], hypertension [1.45 (1.18-1.77)], atrial fibrillation [2.42 (1.51-3.88)], heart failure [2.74 (1.62-4.61)], and smoking [1.40 (1.10-1.79)]. The resulting risk prediction score, incorporating the above seven factors, named CART-7, ranges from 0 to 33, with a score of 0-8 indicating low risk, 9-17 moderate risk, 18-25 high risk, and 26-33 very high risk.
Seven baseline CV conditions were significantly associated with CAR-T cell-related CVAE. Further validation of the resulting CART-7 score is warranted to support its clinical use in baseline CV risk stratification for patients undergoing CAR-T cell therapy.
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