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IF 3.6 3区医学 Q2 HEMATOLOGY

Transplantation and Cellular Therapy Pub Date : 2024-12-11 DOI:10.1016/j.jtct.2024.12.002

Moataz Ellithi, Magdi Elsallab, Matthew A Lunning, Sarah A Holstein, Smriti Sharma, Jonathan Q Trinh, Jihyun Ma, Marcela V Maus, Matthew J Frigault, Christopher R D'Angelo

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引用次数: 0

摘要

背景：嵌合抗原受体T（CAR T）细胞疗法已成为浆细胞疾病患者的一种重要治疗方式。随着接受 CAR T 疗法的患者人数不断增加，识别和处理相关的罕见毒性变得越来越重要：目的：利用食品药品管理局不良事件报告系统（FAERS）识别与商业化抗B细胞成熟抗原（BCMA）CAR T疗法相关的安全信号：这是一项横断面分析，研究对象是2021年1月至2023年12月期间向FAERS提交的与ciltacabtagene autoleucel（cilta-cel）和idecabtagene vicleucel（ide-cel）相关的不良事件（AE）报告。采用描述性统计方法总结了AE频率，并通过测量与对照组相比的报告几率比（ROR）探讨了安全性信号：在4,472,782份FAERS报告中，有1,496份涉及BCMA引导的CAR-T疗法。报告较多的不良反应包括免疫相关疾病和神经系统疾病。与cilta-cel相关的神经毒性主要表现为颅神经麻痹、帕金森氏症、急性和慢性多发性神经病，而ide-cel神经毒性则表现为精神错乱、定向障碍、癫痫发作、平衡障碍和震颤。在cilta-cel的报告中，其他安全信号包括格林-巴利综合征（ROR：17.1，95% CI 6.1-47.5）、颅内出血和脑血管意外（ROR：2.9，95% CI 1.8-4.8）、嗜血杆菌感染（ROR：34.2，95% CI 11.8-98.9）和巨细胞病毒感染（ROR：3.9，95% CI 1.6-9.5）。对于 ide-cel，新信号包括帕金森病（ROR：13.7，95% CI 5.5-34.5）、急性和慢性肉样瘤病（ROR：197.1，95% CI 32.9-1180.1）、室性心律失常和心脏骤停（ROR：3.9，95% CI 2.1-7.3）：这些数据全面揭示了BCMA定向CAR T商用疗法的安全性特征，强调了上市后警惕监测以降低潜在风险的重要性。

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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Neurotoxicity and Rare Adverse Events in BCMA-Directed CAR T Cell Therapy: A Comprehensive Analysis of Real-World FAERS Data.

Background: Chimeric antigen receptor T (CAR T) cell therapies have emerged as a valuable treatment modality for patients with plasma cell disorders. As the population of patients receiving CAR T therapies grows, identification and management of associated rare toxicities have become increasingly crucial.

Objective: To identify safety signals associated with commercial anti-B-cell maturation antigen (BCMA) CAR T therapies using the Food and Drug Administration Adverse Event Reporting System (FAERS).

Study design: This is a cross-sectional analysis of the adverse events (AE) reports associated with ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel), submitted to FAERS between January 2021 and December 2023. AE frequencies were summarized using descriptive statistics, and safety signals were explored by measuring the reporting odds ratio (ROR) compared to control groups.

Results: Among 4,472,782 unique FAERS reports, 1,496 involved BCMA-directed CAR-T therapies. AEs reported more frequently included immune associated conditions and neurological disorders. Neurotoxicity associated with cilta-cel predominantly manifested as cranial nerve palsies, parkinsonism, acute and chronic polyneuropathies, while ide-cel neurotoxicity presented as confusion, disorientation, seizures, balance disturbances, and tremors. In cilta-cel reports, other safety signals included Guillain-Barre syndrome (ROR: 17.1, 95% CI 6.1 -47.5), intracranial hemorrhage and cerebrovascular accidents (ROR: 2.9, 95% CI 1.8 -4.8), haemophilus infections (ROR: 34.2, 95% CI 11.8-98.9) and cytomegalovirus infections (ROR: 3.9, 95% CI 1.6 -9.5). For ide-cel, new signals included parkinsonism (ROR: 13.7, 95% CI 5.5-34.5), acute and chronic sarcoidosis (ROR: 197.1, 95% CI 32.9 -1180.1), ventricular arrhythmias, and cardiac arrest (ROR: 3.9, 95% CI 2.1-7.3).

Conclusion: This data provides a comprehensive insight into the safety profiles of the commercial BCMA-directed CAR T therapies, underscoring the importance of vigilant post-marketing surveillance to mitigate potential risks.

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