文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期，新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

嵌合抗原受体 T 细胞疗法引起的神经系统毒性：基于 FDA 不良事件报告系统数据库的真实世界研究。

Chimeric antigen receptor T-cell therapy-induced nervous system toxicity: a real-world study based on the FDA Adverse Event Reporting System database.

机构信息

Department of Pharmacy, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Pharmacy, Peking University Cancer Hospital & Institute, Beijing, China.

出版信息

BMC Cancer. 2024 Jan 2;24(1):10. doi: 10.1186/s12885-023-11753-x.

DOI:10.1186/s12885-023-11753-x
PMID:38166723
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10762809/
Abstract

BACKGROUND: Nervous system toxicity (NST) is one of the most frequent and dangerous side effects of chimeric antigen receptor T-cell (CAR-T) therapy, which is an effective treatment for related tumors in most relapsed/refractory (r/r) hematologic malignancies. Current clinical trial data do not fully reflect the real-world situation. Therefore, this study evaluated the NST of CAR-T therapy using the FDA Adverse Event Reporting System (FAERS). METHODS: Data were retrieved from FAERS for the period from January 1, 2017 to March 31, 2023. Disproportionality analysis and Bayesian analysis were used for data mining. The reporting odds ratio (ROR) for NST with 95% confidence interval (CI) was calculated for each CAR-T product. The time to onset (TTO) and clinical outcomes due to CAR-T therapy-associated NST were assessed. RESULTS: Overall, 6946 cases of NST associated with CAR-T therapy were identified. The patients had a median age of 61 years (interquartile range [IQR]: 47-69 years). Significant signals were observed for all CAR-T products (ROR: 2.19, 95% CI: 2.13-2.44). Anti-CD19 CAR-T products showed a higher NST signal than anti-B cell maturation antigen (BCMA) CAR-T products (ROR 2.13 vs. 1.98). Brexucabtagene autoleucel (ROR: 3.17, 95% CI: 2.90-3.47) and axicabtagene ciloleucel (ROR: 2.92, 95% CI: 2.81-3.03) had the two highest NST signals. For the preferred term "brain edema," the highest signals were obtained for CD28 CAR-T products. The median TTO of NST for all CAR-T products was 7 days (IQR: 3-17 days). The proportion of death, life-threatening and hospitalization adverse events associated with NST was 20.06%, 7.21%, and 32.70%, respectively. The proportion of death outcomes was higher in patients treated with tisagenlecleucel (30.36%) than in those treated with other CAR-T products, except ciltacabtagene autoleucel (P < 0.001). The proportion of hospitalizations was significantly higher for lisocabtagene maraleucel-associated NST (53.85%) than for other drugs, except for ciltacabtagene autoleucel (P < 0.001). CONCLUSIONS: NST is more closely associated with anti-CD19 CAR-Ts and CAR-Ts containing CD28. Serious NST (brain oedema) is likely to occur with CAR-Ts that contain CD28. CAR-T-related NST warrants greater attention owing to the high proportion of serious adverse events and delayed NST.

摘要

背景：嵌合抗原受体 T 细胞（CAR-T）疗法是治疗相关肿瘤的有效方法，可用于大多数复发/难治性（r/r）血液恶性肿瘤，但该疗法的神经系统毒性（NST）是最常见和最危险的副作用之一。目前的临床试验数据不能完全反映真实世界的情况。因此，本研究使用美国食品药品监督管理局不良事件报告系统（FAERS）评估了 CAR-T 治疗的 NST。

方法：从 FAERS 中检索了 2017 年 1 月 1 日至 2023 年 3 月 31 日的数据。使用比例失调分析和贝叶斯分析进行数据挖掘。计算了每个 CAR-T 产品的 NST 报告比值比（ROR）及其 95%置信区间（CI）。评估了与 CAR-T 治疗相关的 NST 的发病时间（TTO）和临床结局。

结果：共发现 6946 例与 CAR-T 治疗相关的 NST 病例。患者的中位年龄为 61 岁（四分位距 [IQR]：47-69 岁）。所有 CAR-T 产品均显示出显著的信号（ROR：2.19，95%CI：2.13-2.44）。抗 CD19 CAR-T 产品比抗 B 细胞成熟抗原（BCMA）CAR-T 产品显示出更高的 NST 信号（ROR 2.13 比 1.98）。Brexucabtagene autoleucel（ROR：3.17，95%CI：2.90-3.47）和 axicabtagene ciloleucel（ROR：2.92，95%CI：2.81-3.03）具有两种最高的 NST 信号。对于首选术语“脑水肿”，CD28 CAR-T 产品的信号最高。所有 CAR-T 产品的 NST 中位 TTO 为 7 天（IQR：3-17 天）。与 NST 相关的死亡、危及生命和住院不良事件的比例分别为 20.06%、7.21%和 32.70%。与其他 CAR-T 产品相比，tisagenlecleucel 治疗患者的死亡结局比例（30.36%）更高，除 cilta cabtagene autoleucel 外（P<0.001）。与其他药物相比，lisocabtagene maraleucel 相关的 NST 住院比例（53.85%）明显更高，除 cilta cabtagene autoleucel 外（P<0.001）。

结论：NST 与抗 CD19 CAR-T 和含有 CD28 的 CAR-T 更为密切相关。严重的 NST（脑水肿）可能发生在含有 CD28 的 CAR-T 中。由于严重不良事件的比例较高且 NST 延迟，CAR-T 相关的 NST 值得更多关注。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a40/10762809/50099fb69627/12885_2023_11753_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a40/10762809/a326d24f9eb3/12885_2023_11753_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a40/10762809/71bbf0c5dc87/12885_2023_11753_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a40/10762809/482856d8e2ca/12885_2023_11753_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a40/10762809/50099fb69627/12885_2023_11753_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a40/10762809/a326d24f9eb3/12885_2023_11753_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a40/10762809/71bbf0c5dc87/12885_2023_11753_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a40/10762809/482856d8e2ca/12885_2023_11753_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a40/10762809/50099fb69627/12885_2023_11753_Fig4_HTML.jpg

相似文献

[1]
Chimeric antigen receptor T-cell therapy-induced nervous system toxicity: a real-world study based on the FDA Adverse Event Reporting System database.

BMC Cancer. 2024-1-2

[2]
Neurotoxicity associated with chimeric antigen receptor T-cell therapy: a real-world study leveraging the FDA Adverse Event Reporting System.

Expert Opin Drug Saf. 2024-10-16

[3]
Dermatologic Adverse Events Associated With Chimeric Antigen Receptor T-Cell Therapy: A Pharmacovigilance Analysis of the FDA Reporting System.

Transplant Cell Ther. 2024-10

[4]
Safety assessment of anti-B cell maturation antigen chimeric antigen receptor T cell therapy: a real-world study based on the FDA adverse event reporting system database.

Front Immunol. 2024

[5]
Updated insights on cardiac risks of CD19-directed chimeric antigen receptor T-cell therapy: a pharmacovigilance study.

Immunotherapy. 2023-4

[6]
Safety profile of chimeric antigen receptor T-cell immunotherapies (CAR-T) in clinical practice.

Eur J Clin Pharmacol. 2021-8

[7]
Impact of Manufacturing Procedures on CAR T Cell Functionality.

Front Immunol. 2022

[8]
Comparing the Differences in Adverse Events among Chimeric Antigen Receptor T-Cell Therapies: A Real-World Pharmacovigilance Study.

Pharmaceuticals (Basel). 2024-8-5

[9]
Late relapse after CAR-T cell therapy for adult patients with hematologic malignancies: A definite evidence from systematic review and meta-analysis on individual data.

Pharmacol Res. 2023-4

[10]
Efficacy and safety of CD19-directed CAR-T cell therapies in patients with relapsed/refractory aggressive B-cell lymphomas: Observations from the JULIET, ZUMA-1, and TRANSCEND trials.

Am J Hematol. 2021-10-1

引用本文的文献

[1]
Effects of non-contact electric fields on the kidneys and livers of tumour-bearing rats.

F1000Res. 2025-2-11

[2]
Chimeric antigen receptor T-cell therapy in patients with malignant glioma-From neuroimmunology to clinical trial design considerations.

Neuro Oncol. 2025-2-10

[3]
Neurofilament light chain levels as an early predictive biomarker of neurotoxicity after CAR T-cell therapy.

J Immunother Cancer. 2024-9-24

本文引用的文献

[1]
The pathogenesis, diagnosis, prevention, and treatment of CAR-T cell therapy-related adverse reactions.

Front Pharmacol. 2022-10-14

[2]
Clinical Presentation, Risk Factors, and Outcomes of Immune Effector Cell-Associated Neurotoxicity Syndrome Following Chimeric Antigen Receptor T Cell Therapy: A Systematic Review.

Transplant Cell Ther. 2022-6

[3]
Mechanisms of cytokine release syndrome and neurotoxicity of CAR T-cell therapy and associated prevention and management strategies.

J Exp Clin Cancer Res. 2021-11-18

[4]
Efficacy and safety of CD19-directed CAR-T cell therapies in patients with relapsed/refractory aggressive B-cell lymphomas: Observations from the JULIET, ZUMA-1, and TRANSCEND trials.

Am J Hematol. 2021-10-1

[5]
Pericardial Toxicities Associated With Immune Checkpoint Inhibitors: A Pharmacovigilance Analysis of the FDA Adverse Event Reporting System (FAERS) Database.

Front Pharmacol. 2021-7-2

[6]
Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study.

Lancet. 2021-7-24

[7]
KTE-X19 for relapsed or refractory adult B-cell acute lymphoblastic leukaemia: phase 2 results of the single-arm, open-label, multicentre ZUMA-3 study.

Lancet. 2021-8-7

[8]
Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma.

N Engl J Med. 2021-2-25

[9]
Cytokines in CAR T Cell-Associated Neurotoxicity.

Front Immunol. 2020

[10]
Relmacabtagene autoleucel (relma-cel) CD19 CAR-T therapy for adults with heavily pretreated relapsed/refractory large B-cell lymphoma in China.

Cancer Med. 2021-2

文献AI研究员

20分钟写一篇综述，助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索