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复发性滤泡性淋巴瘤伴大量乳糜性腹水对使用 Piggy Bac 的抗 CD19 CAR-T 治疗快速缓解:1 例病例报告

英文原题:Rapid response in relapsed follicular lymphoma with massive chylous ascites to anti-CD19 CAR T therapy using Piggy Bac: A case report.

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Rapid response in relapsed follicular lymphoma with massive chylous ascites to anti-CD19 CAR T therapy using Piggy Bac: A case report.

PubMed 2022/12/01(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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中文摘要

CD19靶向嵌合抗原受体(CAR)T细胞疗法已被证明在难治性或复发性B细胞非霍奇金淋巴瘤患者中可实现相当持久的缓解,Zuma-1、Zuma-5及其他临床试验结果均显示了这一点。这些CAR大多通过慢病毒或逆转录腺病毒制备。使用非病毒载体(如Piggy Bac,pb)的CAR用于治疗活动性疾病的淋巴瘤患者较为罕见。一般而言,如文献报道,高肿瘤负荷的患者往往有更高的严重细胞因子释放综合征(CRS)或神经系统事件发生率。有症状性胸腔积液的患者因存在严重CRS风险而被排除在Zuma-1试验之外。

我们在此报告一例复发性滤泡性淋巴瘤患者,伴有大块病灶和大量乳糜性腹水,多线化疗失败。在输注CD19靶向pbCAR-T 细胞6×10^6 cells/kg后,患者迅速获得缓解,并在第28天达到近乎完全代谢缓解。仅发生1级CRS,未出现神经毒性。CAR-T 细胞在第14天达到峰值水平,并扩散至腹水中,持续扩增3个月。这可能是首例报道的pbCAR-T 细胞直接治疗复发性滤泡性淋巴瘤的病例。长期疗效有待观察,未来将有更多患者接受测试。临床试验注册:https://ClinicalTrials.gov,标识符NCT05472610。

展开英文摘要原文

UNLABELLED: CD19-directed chimeric antigen receptor (CAR) T cell therapy has been shown to achieve a considerably durable response in patients with refractory or relapsed B cell non-Hodgkin lymphomas, as seen from the results of Zuma-1, Zuma-5, and other clinical trials. Most of these CARs were generated by lentivirus or reverse adenovirus.

It is rare to see CARs using non-viral vectors, such as Piggy Bac (pb), in treating lymphoma patients with active diseases. Generally, patients with a high tumor burden tend to have a higher rate of severe cytokine release syndrome (CRS) or neurological events as reported in the literature. Patients with symptomatic pleural effusions are excluded from the Zuma-1 trial because of the risk of severe CRS.

We report here that a patient with relapsed follicular lymphoma with bulky disease and massive chylous ascites failed several lines of chemotherapy. After infusion of the CD19-directed pbCAR-T cells at 6 10 6 cells/kg, the patient had a rapid response and achieved a nearly complete metabolic remission on day 28. There was only grade 1 CRS, and no neurotoxicity occurred.

The CAR-T cells reached a peak level on day 14 and spread into the ascites and expanded for 3 months. This might be the first case reported for pbCAR-T cells to treat relapsed follicular lymphoma directly. The long-term efficacy will be observed, and more patients be tested in the future. CLINICAL TRIAL REGISTRATION: https://ClinicalTrials. gov, identifier NCT05472610.

论文信息

作者
Zhang Y、Lin Z、Zhang F、Chen X、Yang Y、Fu X、Li Z、Sun Y
单位
Department of Oncology, Shanghai Mengchao Cancer Hospital, Shanghai University, Shanghai, China.China
文献类型
病例报告 · 非美国政府资助研究
期刊
Frontiers in immunology2022
原文标识
PubMed 36532014 · DOI 10.3389/fimmu.2022.1007210