Cardiovascular toxicities associated with bispecific T-cell engager therapy.
Cardiovascular toxicities associated with bispecific T-cell engager therapy.
复制标题
与双特异性 T 细胞接合疗法相关的心血管毒性。
DOI：
10.1136/jitc-2023-008518
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发表时间：
2024
影响因子：
10.9
通讯作者：
Epp
中科院分区：
文献类型：
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作者：
Sayed,Ahmed;Munir,Malak;Ghazi,SanamM;Ferdousi,Mussammat;Krishan,Satyam;Shaaban,Adnan;Habib,Alma;Kola-Kehinde,Onaopepo;Ruz,Patrick;Khan,Sarah;Sharma,Sneha;Meara,Alexa;Mahmood,Syed;Feldman,Stephanie;Yang,EricH;Kim,Jiwon;Epp
背景双特异性t细胞接合剂（BTEs）是一种用于治疗血液系统恶性肿瘤的新型药物。早期试验不足以确定心血管不良事件（CVAE），也没有大规模的研究系统地检查与bte相关的CVAEs。方法利用美国食品和药物管理局的不良事件报告系统-(FAERS)，我们确定了2014年至2023年期间美国食品和药物管理局批准用于治疗血液恶性肿瘤的五种BTE产品启动后CVAEs的相对频率。调整报告or （aROR）用于识别与数据库中背景率相比，CVAEs与bte的报告不成比例。计算每种不良事件（AE）的死亡率和风险比（rr）。结果在FAERS报告的3668例bte相关病例中，747例（20.4%）涉及CVAEs。bte作为一个类别与致命性CVAEs相关（aROR为1.29 (95% CI 1.12 - 1.50)），这种关联主要由替司他单抗驱动（aROR为2.44 (95% CI 1.65 - 3.60)）。Teclistamab也与心肌炎（aROR 25.70 (95% CI 9.54至69.23)）和休克（aROR 3.63 (95% CI 2.30至5.74)）的不成比例风险相关，而blinatumab与弥散性血管内凝血（aROR 3.02 (95% CI 1.98至4.60)）和低血压（aROR 1.59 (95% CI 1.25至2.03)）不成比例风险相关。CVAEs比非CVAEs更致命（31.1% vs 17.4%; RR 1.76 (95% CI 1.54 ~ 2.03)）。大多数CVAEs（83.3%）未与细胞因子释放综合征重叠。在首个bte上市后监测研究中，大约五分之一的AE报告涉及CVAEs，并具有显著的死亡风险。
Background Bispecific T-cell engagers (BTEs) are novel agents used to treat hematological malignancies. Early trials were underpowered to define cardiovascular adverse events (CVAE) and no large-scale studies systematically examined the CVAEs associated with BTEs. Methods Leveraging the US Food and Drug Administration’s Adverse Event Reporting System-(FAERS), we identified the relative frequency of CVAEs after initiation of five BTE products approved by the Food and Drug Administration between 2014 and 2023 for the treatment of hematological malignancies. Adjusted reporting ORs (aROR) were used to identify disproportionate reporting of CVAEs with BTEs compared with background rates in the database. Fatality rates and risk ratios (RRs) for each adverse event (AE) were calculated. Results From 3668 BTE-related cases reported to FAERS, 747 (20.4%) involved CVAEs. BTEs as a class were associated with fatal CVAEs (aROR 1.29 (95% CI 1.12 to 1.50)), an association mainly driven by teclistamab (aROR 2.44 (95% CI 1.65 to 3.60)). Teclistamab was also associated with a disproportionate risk of myocarditis (aROR 25.70 (95% CI 9.54 to 69.23)) and shock (aROR 3.63 (95% CI 2.30 to 5.74)), whereas blinatumomab was associated with a disproportionate risk of disseminated intravascular coagulation (aROR 3.02 (95% CI 1.98 to 4.60)) and hypotension (aROR 1.59 (95% CI 1.25 to 2.03)). CVAEs were more fatal compared with non-CVAEs (31.1% vs 17.4%; RR 1.76 (95% CI 1.54 to 2.03)). Most CVAEs (83.3%) did not overlap with cytokine release syndrome. Conclusion In the first postmarketing surveillance study of BTEs, CVAEs were involved in approximately one in five AE reports and carried a significant mortality risk.