CD19与BCMA靶向CAR-T药物不良反应的真实世界药物警戒研究

路璐; 安鹏姣; 许治清; 赵彬

doi:10.12290/xhyxzz.2025-0755

CD19与BCMA靶向CAR-T药物不良反应的真实世界药物警戒研究

A Real-World Pharmacovigilance Study of Adverse Drug Reactions to CD19- and BCMA-Targeted CAR-T Cell Therapies

摘要

摘要:
目的评价4种以CD19为靶点和2种以BCMA为靶点的嵌合抗原受体T(chimeric antigen receptor T, CAR-T)药物的临床安全性。
方法检索2004年1月—2025年3月美国食品药品监督管理局不良事件报告系统数据库中6种CAR-T(Breyanzi、Kymriah、Tecartus、Yescarta、Abecma、Carvykti)相关药物不良反应(adverse drug reactions, ADRs)报告, 分析报告的基本特征, 根据系统器官分类(system organ class, SOC) 术语对ADRs进行分类, 并采用国际医学用语词典(V27.1)将报告中的ADRs编码为相应的首选术语(preferred term, PT)。采用报告比值比(reporting odds ratio, ROR)和比例报告比(proportional reporting ratio, PRR)挖掘6种药物与PT的关联信号。
结果共纳入54 833例ADRs报告, 其中Breyanzi 1511例(2.76%)、Kymriah 18 087例(32.99%)、Tecartus 4408例(8.04%)、Yescarta 23 937例(43.65%)、Abecma 2762例(5.04%)、Carvykti 4128例(7.53%)。共15 210例患者纳入本研究, 其中男性7136例(46.92%), 女性4483例(29.47%), 3591例(23.61%)性别信息缺失。年龄分布方面, Abecma和Carvykti组患者年龄均≥18岁, 而Kymriah组患者中年龄＜18岁的比例为22.52%。性别分布方面, 6组患者中男性比例均高于女性。报告数量排名前7位的ADRs依次为各类神经系统疾病、免疫系统疾病、全身性疾病及给药部位各种反应、各类检查、感染及侵染类疾病、各类肿瘤以及血液和淋巴系统疾病。6种CAR-T药物ADRs报告数量排名前10位的PT包括细胞因子释放综合征(cytokine release syndrome, CRS)、免疫效应细胞相关性神经毒性综合征(immune effector cell-associated neurotoxicity syndrome, ICANS)、发热、神经毒性、死亡、低血压、疾病进展、疲劳、血小板计数降低和恶性肿瘤进展。6种CAR-T药物中, BCMA靶向的Abecma与CRS的关联性最强ROR值为2412.12(95% CI: 2093.06~2779.83), PRR值为891.75(χ²=449 083.34); CD19靶向的Tecartus与ICANSROR值为2604.50(95% CI: 2317.29~2927.30), PRR值为1775.36(χ²=705 195.47)及神经毒性ROR值为762.84(95% CI: 685.77~848.56), PRR值为439.88(χ²=254 246.08)的关联性最强。除Tecartus外, 其余5种药物均与血小板计数降低存在关联信号。此外, Breyanzi和Kymriah均与恶性肿瘤进展存在关联信号。
结论临床医生应对接受CAR-T治疗的患者进行严密的安全性管理, 尤其关注CRS和神经毒性的早期症状, 并加强对恶性肿瘤进展的监测。

Abstract:
Objective To evaluate the clinical safety of four CD19-targeted and two BCMA-targeted chimeric antigen receptor T-cell (CAR-T) therapies.
Methods Adverse drug reaction (ADR) reports for six CAR-T products (Breyanzi, Kymriah, Tecartus, Yescarta, Abecma, Carvykti) from the US FDA Adverse Event Reporting System (FAERS) database between January 2004 and March 2025 were retrieved. The basic characteristics of the reports were analyzed. ADRs were categorized by System Organ Class (SOC) and coded into corresponding preferred term(PT) using MedDRA (Version 27.1). The reporting odds ratio (ROR) and proportional reporting ratio (PRR) methods were used to detect association signals between the six drugs and the PT.
Results A total of 54 833 ADR reports were included in this study: Breyanzi (1511, 2.76%), Kymriah (18 087, 32.99%), Tecartus (4408, 8.04%), Yescarta (23 937, 43.65%), Abecma (2762, 5.04%), and Carvykti (4128, 7.53%). These reports corresponded to 15 210 unique patients, comprising 7136 males (46.92%), 4483 females (29.47%), and 3591 (23.61%) with missing gender information. Regarding age distribution, all patients in the Abecma and Carvykti groups were ≥18 years old, while 22.52% of patients in the Kymriah group were < 18 years old. The proportion of male patients was higher than that of females across all six drug groups. The top seven ADRs by report count were, in order: various nervous system disorders; immune system disorders; general disorders and administration site conditions; various investigations; infections and infestations; various neoplasms; and blood and lymphatic system disorders. The top ten PTs by report count included cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), pyrexia, neurotoxicity, death, hypotension, disease progression, fatigue, platelet count decreased, and malignant neoplasm progression. Among the six CAR-T therapies, the BCMA-targeted Abecma showed the strongest association with CRS ROR 2412.12(95% CI: 2093.06-2779.83), PRR 891.75(χ²=449 083.34). The CD19-targeted Tecartus showed the strongest association with ICANS ROR 2604.50 (95% CI: 2317.29-2927.30), PRR 1775.36 (χ²=705 195.47) and neurotoxicity ROR 762.84(95% CI: 685.77-848.56), PRR 439.88 (χ²=254 246.08).All drugs except Tecartus were associated with decreased platelet count. Furthermore, both Breyanzi and Kymriah were associated with malignant neoplasm progression.
Conclusions Clinicians should implement rigorous safety monitoring for patients receiving CAR-T therapy, paying particular attention to the early symptoms of CRS and neurotoxicity, and enhance surveillance for malignant neoplasm progression.

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