Unit of Pharmacology, Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, via Irnerio 48, 40126, Bologna, Italy.
Pharmacology at the Alma Mater Studiorum, University of Bologna, Bologna, Italy.
Eur J Clin Pharmacol. 2021 Aug;77(8):1225-1234. doi: 10.1007/s00228-021-03106-z. Epub 2021 Feb 20.
Two chimeric antigen receptor T-cell (CAR-T) therapies have been approved in the United States (USA) in 2017 and Europe (EU) in 2018: axicabtagene ciloleucel and tisagenlecleucel. They contain the patient's own T cells, which are extracted, genetically modified, and reinfused. Alongside the good efficacy results, the assessment of safety profile of these new therapies represents a great challenge. Our aim was to analyze the reports of the adverse drug reactions (ADR) after CAR-T administration as occurred in the real clinical setting.
We performed a retrospective observational study, collecting all the reports in EU (EudraVigilance, EV) and US (FAERS) databases of ADRs regarding axicabtagene ciloleucel and tisagenlecleucel. Both descriptive and statistical analyses were performed, the latter by using Reporting Odds Ratio (ROR).
A total number of 1426 reports of suspected ADRs were retrieved in EudraVigilance and FAERS. Patients' reported age reflected the age range for which the drugs are approved (18-64 years for axicabtagene ciloleucel and patients aged under 25 years for tisagenlecleucel). The most reported event was cytokine release syndrome (CRS), 185 events for tisagenlecleucel and 462 for axicabtagene ciloleucel in FAERS and 137 and 498, respectively, in EudraVigilance. A disproportionality was found comparing axicabtagene ciloleucel with tisagenlecleucel for the above-mentioned event: EV ROR 2.47, 95% CI 2.22-2.74, FAERS 1.89, 1.70-2.10.
CRS represents the major problem with the administration of CAR-T therapies. Our analysis has not revealed new ADRs; however, it supports the safety profile of CAR-T with new data from real clinical setting.
两种嵌合抗原受体 T 细胞（CAR-T）疗法于 2017 年在美国（美国）和 2018 年在欧洲（欧盟）获得批准：axicabtagene ciloleucel 和 tisagenlecleucel。它们包含患者自身的 T 细胞，这些 T 细胞被提取、基因修饰并重新注入。除了良好的疗效结果外，评估这些新疗法的安全性概况也是一项巨大的挑战。我们的目的是分析在真实临床环境中 CAR-T 给药后不良药物反应（ADR）报告。
我们进行了一项回顾性观察性研究，收集了欧盟（EudraVigilance，EV）和美国（FAERS）数据库中关于 axicabtagene ciloleucel 和 tisagenlecleucel 的 ADR 报告，进行了描述性和统计分析，后者使用报告比值比（ROR）。
在 EudraVigilance 和 FAERS 中检索到了 1426 份可疑 ADR 报告。患者报告的年龄反映了药物批准的年龄范围（axicabtagene ciloleucel 为 18-64 岁，tisagenlecleucel 为 25 岁以下的患者）。报告最多的事件是细胞因子释放综合征（CRS），FAERS 中 tisagenlecleucel 为 185 例，axicabtagene ciloleucel 为 462 例，EudraVigilance 中分别为 137 例和 498 例。在上述事件中，axicabtagene ciloleucel 与 tisagenlecleucel 相比发现了不成比例性：EV ROR 2.47，95%CI 2.22-2.74，FAERS 1.89，1.70-2.10。
CRS 是 CAR-T 治疗给药的主要问题。我们的分析没有发现新的 ADR，但它支持了 CAR-T 的安全性概况，并提供了来自真实临床环境的新数据。
