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抗 CD19 CAR T 治疗复发滤泡性淋巴瘤合并大量乳糜性腹水的快速反应:病例报告。

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

机构信息

Department of Oncology, Shanghai Mengchao Cancer Hospital, Shanghai University, Shanghai, China.

Clinical R&D Center, Shanghai Cell Therapy Group Corporation, Shanghai, China.

出版信息

Front Immunol. 2022 Dec 1;13:1007210. doi: 10.3389/fimmu.2022.1007210. eCollection 2022.

Abstract

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 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.

摘要

未注明

嵌合抗原受体 (CAR) T 细胞疗法靶向 CD19 已在难治性或复发性 B 细胞非霍奇金淋巴瘤患者中显示出显著持久的反应,这从 Zuma-1、Zuma-5 和其他临床试验结果中可以看出。这些 CAR 大多由慢病毒或反向腺病毒产生。在治疗患有活动性疾病的淋巴瘤患者时,使用非病毒载体(如 PiggyBac(pb))的 CAR 很少见。通常,高肿瘤负荷的患者往往会出现更高的严重细胞因子释放综合征 (CRS) 或神经事件发生率,这在文献中有报道。由于严重 CRS 的风险,有症状性胸腔积液的患者被排除在 Zuma-1 试验之外。我们在此报告一例复发滤泡性淋巴瘤伴大肿块疾病和大量乳糜性腹水的患者,该患者在几线化疗后均失败。在输注 6×10 个/kg 的靶向 CD19 的 pbCAR-T 细胞后,患者迅速反应,在第 28 天达到几乎完全代谢缓解。仅发生 1 级 CRS,未发生神经毒性。CAR-T 细胞在第 14 天达到峰值水平,并扩散到腹水并扩展 3 个月。这可能是首例报告使用 pbCAR-T 细胞直接治疗复发性滤泡性淋巴瘤的病例。将观察长期疗效,并在未来对更多患者进行测试。

临床试验注册

https://ClinicalTrials.gov,标识符 NCT05472610。

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