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嵌合抗原受体T细胞(CAR-T)疗法的肺部不良事件概况:一项基于FDA不良事件报告系统(FAERS)数据库(2017 - 2023年)的药物警戒研究。

CAR-T therapy pulmonary adverse event profile: a pharmacovigilance study based on FAERS database (2017-2023).

作者信息

Shi Jing, Liu Xinya, Jiang Yun, Gao Mengjiao, Yu Jian, Zhang Yuanming, Wu Li

机构信息

Xinjiang Medical University, Urumqi, China.

Department of Oncology Cardiology, Xinjiang Medical University Cancer Hospital, Urumqi, China.

出版信息

Front Pharmacol. 2024 Aug 21;15:1434231. doi: 10.3389/fphar.2024.1434231. eCollection 2024.


DOI:10.3389/fphar.2024.1434231
PMID:39234101
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11371680/
Abstract

BACKGROUND: Chimeric antigen receptor T-cell (CAR-T) therapy, a rapidly emerging treatment for cancer that has gained momentum since its approval by the FDA in 2017, involves the genetic engineering of patients' T cells to target tumors. Although significant therapeutic benefits have been observed, life-threatening adverse pulmonary events have been reported. METHODS: Using SAS 9.4 with MedDRA 26.1, we retrospectively analyzed data from the Food and Drug Administration's Adverse Event Reporting System (FAERS) database, covering the period from 2017 to 2023. The analysis included the Reporting Odds Ratio Proportional Reporting Ratio Information Component and Empirical Bayes Geometric Mean to assess the association between CAR-T cell therapy and adverse pulmonary events (PAEs). RESULTS: The FAERS database recorded 9,400 adverse events (AEs) pertaining to CAR-T therapies, of which 940 (10%) were PAEs. Among these CAR-T cell-related AEs, hypoxia was the most frequently reported (344 cases), followed by respiratory failure (127 cases). Notably, different CAR-T cell treatments demonstrated varying degrees of association with PAEs. Specifically, Tisa-cel was associated with severe events including respiratory failure and hypoxia, whereas Axi-cel was strongly correlated with both hypoxia and tachypnea. Additionally, other CAR-T therapies, namely, Brexu-cel, Liso-cel, Ide-cel, and Cilta-cel, have also been linked to distinct PAEs. Notably, the majority of these PAEs occurred within the first 30 days post-treatment. The fatality rates varied among the different CAR-T therapies, with Tisa-cel exhibiting the highest fatality rate (43.6%), followed by Ide-cel (18.8%). CONCLUSION: This study comprehensively analyzed the PAEs reported in the FAERS database among recipients of CAR-T cell therapy, revealing conditions such as hypoxia, respiratory failure, pleural effusion, and atelectasis. These CAR-T cell therapy-associated events are clinically significant and merit the attention of clinicians and researchers.

摘要

背景:嵌合抗原受体T细胞(CAR-T)疗法是一种迅速兴起的癌症治疗方法,自2017年获得美国食品药品监督管理局(FDA)批准以来发展势头迅猛,该疗法涉及对患者T细胞进行基因工程改造以靶向肿瘤。尽管已观察到显著的治疗益处,但有危及生命的肺部不良事件的报告。 方法:我们使用SAS 9.4和MedDRA 26.1,对美国食品药品监督管理局不良事件报告系统(FAERS)数据库中2017年至2023年期间的数据进行回顾性分析。分析包括报告比值比、比例报告比信息成分和经验贝叶斯几何均值,以评估CAR-T细胞疗法与肺部不良事件(PAE)之间的关联。 结果:FAERS数据库记录了9400例与CAR-T疗法相关的不良事件(AE),其中940例(10%)为PAE。在这些与CAR-T细胞相关的AE中,低氧是报告最频繁的(344例),其次是呼吸衰竭(127例)。值得注意的是,不同的CAR-T细胞治疗与PAE表现出不同程度的关联。具体而言,Tisagenlecleucel与包括呼吸衰竭和低氧在内的严重事件相关,而Axicabtagene ciloleucel与低氧和呼吸急促均密切相关。此外,其他CAR-T疗法,即Breyanzi、Lisocabtagene maraleucel、Idecabtagene vicleucel和Ciltacabtagene autoleucel,也与不同的PAE有关。值得注意的是,这些PAE大多发生在治疗后的前30天内。不同CAR-T疗法的死亡率各不相同,Tisagenlecleucel的死亡率最高(43.6%),其次是Idecabtagene vicleucel(18.8%)。 结论:本研究全面分析了FAERS数据库中CAR-T细胞疗法接受者报告的PAE,揭示了低氧、呼吸衰竭、胸腔积液和肺不张等情况。这些与CAR-T细胞疗法相关的事件具有临床意义,值得临床医生和研究人员关注。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d48/11371680/172e51a9444a/fphar-15-1434231-g007.jpg
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本文引用的文献

[1]
Cardiovascular toxicity induced by SSRIs: Analysis of spontaneous reports submitted to FAERS.

Psychiatry Res. 2023-8

[2]
Two cases of severe pulmonary toxicity from highly active mesothelin-directed CAR T cells.

Mol Ther. 2023-8-2

[3]
CAR-T Cell Therapy: the Efficacy and Toxicity Balance.

Curr Hematol Malig Rep. 2023-4

[4]
Brexucabtagene Autoleucel for Relapsed or Refractory Mantle Cell Lymphoma in Standard-of-Care Practice: Results From the US Lymphoma CAR T Consortium.

J Clin Oncol. 2023-5-10

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Serious adverse events and coping strategies of CAR-T cells in the treatment of malignant tumors.

Front Immunol. 2022

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GLP-1 receptor agonist-associated tumor adverse events: A real-world study from 2004 to 2021 based on FAERS.

Front Pharmacol. 2022-10-25

[7]
Ciltacabtagene Autoleucel, an Anti-B-cell Maturation Antigen Chimeric Antigen Receptor T-Cell Therapy, for Relapsed/Refractory Multiple Myeloma: CARTITUDE-1 2-Year Follow-Up.

J Clin Oncol. 2023-2-20

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Cell. 2022-5-12

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Adverse Event Profiles of PARP Inhibitors: Analysis of Spontaneous Reports Submitted to FAERS.

Front Pharmacol. 2022-3-25

[10]
KIR2DS1-HLA-C status as a predictive marker for benefit from rituximab: a post-hoc analysis of the RICOVER-60 and CLL8 trials.

Lancet Haematol. 2022-2

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