Post-marketing Safety Assessment of CAR T-cell Therapies: Analysis of Individual Case Safety Reports in the VigiBase.

IF 1.9 4区医学 Q4 MEDICAL INFORMATICS

Therapeutic innovation & regulatory science Pub Date : 2025-07-21 DOI:10.1007/s43441-025-00826-7

Meshael M AlRasheed, Solaiman M AlHawas, Nora N AlOrf, Nouf S AlFadel, Fawaz F AlHarbi

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引用次数: 0

Abstract

Purpose: Chimeric Antigen Receptor (CAR)-T cell therapies have emerged as potential therapy for hematological malignancies, however, their safety profiles should be monitored after approval. Therefore, we aimed in this study to explore and analyze individual case safety report (ICSRs) associated with CAR-T cell therapies and reported to the World Health Organization (WHO) global database (VigiBase).

Methods: A retrospective pharmacovigilance study was conducted to describe and characterize Adverse drug reactions (ADRs) reported to Vigibase from inception to March 31st, 2024 and associated with use of the following CAR-T cell therapies: Tisagenlecleucel, Axicabtagene ciloleucel, Brexucabtagene autoleucel, Lisocabtagene maraleucel, Idecabtagene vicleucel, and Ciltacabtagene autoleucel.

Results: A total of 11,693 ICSRs were identified with the use of CAR-T cell therapies in VigiBase (Axicabtagene ciloleucel (N = 5668, 48.5%), Tisagenlecleucel (N = 3364, 28.8%), Brexucabtagene autoleucal (N = 1027, 8.8%), Lisocabtagene maraleucel (N = 304, 2.6%), Idecabtagene vicleucel (N = 579, 4.9%), and Ciltacabtagene autoleucel (N = 751, 6.4%)). ICSRs completeness score was averaged between 0.2 and 0.57 among all included products and the majority of reported ADRs were serious (67-91%). Among serious ADRs, death was reported with an average percentage of (8.8-21.5%). The majority of ADR reports with fatal outcome occurred in accordance with their approved indications. About 18% of fatal events reported with Tisagenlecleucel as the suspected drug were in the pediatric population.

Conclusion: Our study provides an overall exploration of the post-marketing safety profiles of currently approved CAR-T cell therapies. The significant proportion of fatalities occurred in accordance with approved indications, emphasizes the need for ongoing investigation into ADRs with fatal outcomes, particularly in the pediatric population.

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CAR - t细胞疗法上市后安全性评估：VigiBase中个例安全性报告分析

目的：嵌合抗原受体(CAR)-T细胞疗法已成为血液系统恶性肿瘤的潜在治疗方法，然而，其安全性应在批准后进行监测。因此，我们在本研究中旨在探索和分析与CAR-T细胞治疗相关的个案安全报告（ICSRs），并报告给世界卫生组织（WHO）全球数据库（VigiBase）。方法：进行回顾性药物警戒研究，描述和表征Vigibase从成立到2024年3月31日报告的与使用以下CAR-T细胞疗法相关的药物不良反应（adr）： Tisagenlecleucel, Axicabtagene ciloleucel, Brexucabtagene autoeucel, Lisocabtagene maraleucel， Idecabtagene vicleucel和Ciltacabtagene autoeucel。结果：使用CAR-T细胞疗法共鉴定出11,693例ICSRs，其中VigiBase (Axicabtagene ciloleucel) （N = 5668例，48.5%）、Tisagenlecleucel （N = 3364例，28.8%）、Brexucabtagene autotolucel （N = 1027例，8.8%）、Lisocabtagene maraleucel （N = 304例，2.6%）、Idecabtagene vicleel （N = 579例，4.9%）和Ciltacabtagene autotolucel （N = 751,6.4%）。所有纳入产品的ICSRs完整性评分平均在0.2 - 0.57之间，大多数报告的adr是严重的（67-91%）。在严重不良反应中，报告死亡的平均百分比为（8.8-21.5%）。大多数具有致命结果的ADR报告是根据其批准的适应症发生的。以Tisagenlecleucel作为疑似药物报道的死亡事件中，约18%发生在儿科人群中。结论：我们的研究对目前批准的CAR-T细胞疗法上市后的安全性进行了全面的探索。根据批准的适应症发生的很大比例的死亡，强调需要对具有致命结果的adr进行持续调查，特别是在儿科人群中。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Therapeutic innovation & regulatory science MEDICAL INFORMATICS-PHARMACOLOGY & PHARMACY

CiteScore

3.40

自引率

13.30%

发文量

127

期刊介绍： Therapeutic Innovation & Regulatory Science (TIRS) is the official scientific journal of DIA that strives to advance medical product discovery, development, regulation, and use through the publication of peer-reviewed original and review articles, commentaries, and letters to the editor across the spectrum of converting biomedical science into practical solutions to advance human health. The focus areas of the journal are as follows: Biostatistics Clinical Trials Product Development and Innovation Global Perspectives Policy Regulatory Science Product Safety Special Populations