肿瘤细胞治疗研究
英文原题：Incidence of immune effector cell-associated neurotoxicity among patients treated with CAR T-cell therapy for hematologic malignancies: systematic review and meta-analysis.
CAR T 细胞疗法相关 ICANS 的总体发生率为全级别 26.9%、高级别 10.5%。
目的：评估血液系统恶性肿瘤嵌合抗原受体（CAR）T细胞治疗临床试验和真实世界研究中免疫效应细胞相关神经毒性综合征（ICANS）的合并发生率，并比较不同药物之间的发生率。 方法：检索PubMed、Embase和Web of Science数据库中的临床试验及真实世界研究。采用逆方差加权模型计算合并发生率并开展亚组分析；采用二项-正态模型进行多变量分析。 结果：共纳入75项试验，涉及3,184例患者。总体合并发生率为：任何级别ICANS 26.9%（95% CI：21.7%–32.7%），高级别ICANS 10.5%（95% CI：8.1%–13.6%）。亚组分析显示，抗CD19药物队列的ICANS发生率显著高于使用其他药物的队列。多变量分析表明，与抗BCMA药物研究相比，抗CD19药物研究中发生高级别ICANS的几率更高（OR=4.6）。在12项真实世界研究中，使用含CD28共刺激结构域的阿基仑赛的研究，任何级别和高级别ICANS发生率分别为54.0%和26.4%，显著高于使用含4-1BB共刺激结构域的替沙格列赛（tisagenlecleucel）研究的17.2%和6.1%。 结论：CAR T细胞治疗中任何级别和高级别ICANS的总体发生率分别为26.9%和10.5%。与其他药物相比，使用抗CD19药物的患者发生高级别ICANS的风险显著增加。因此，应考虑对接受CAR T细胞治疗的患者仔细监测ICANS。
OBJECTIVES: We aim to assess the pooled incidence of immune effector cell-associated neurotoxicity syndrome (ICANS) in clinical trials and real-world studies of chimeric antigen receptor (CAR) T-cell therapy for hematologic malignancy and compare the incidences among different agents. METHODS: The PubMed, Embase, and Web of Science databases were searched for clinical trials and real-world studies. An inverse-variance weighting model was used to calculate pooled incidences and subgroup analyses. Multivariable analysis was conducted using binomial-normal modeling. RESULTS: Seventy-five trials comprising 3,184 patients were included. The overall pooled incidence was 26.9% (95% CI, 21.7-32.7%) for all-grade and 10.5% (95% CI, 8.1-13.6%) for high-grade ICANS. In subgroup analysis, cohorts with anti-CD19 drugs had significantly higher ICANS incidences than cohorts with other agents. The multivariable analysis demonstrated higher odds of ICANS in anti-CD19 drug studies for high-grade (OR, 4.6) compared to anti-BCMA drug studies. In 12 real-world studies, studies used axicabtagene ciloleucel with CD28 (54.0% all-grade, 26.4% high-grade) exhibited significantly higher rates of all-grade and high-grade ICANS than studies using tisagenlecleucel with 4-1BB (17.2% all-grade, 6.1% high-grade). CONCLUSIONS: The overall incidences of ICANS with CAR T-cell therapy were 26.9% for all-grade and 10.5% for high-grade. Compared with other agents, patients with anti-CD19 drugs had a significantly increased risk of developing high-grade ICANS. Therefore, careful monitoring of ICANS should be considered for patients undergoing CAR T-cell therapy.
MEMBER ACCOUNT
登录成功会直接打开下一页。
