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新型抗 CD19 CAR-T 治疗复发性滤泡性淋巴瘤伴假性进展和巨细胞病毒感染的快速反应:一例报告。

Rapid response in relapsed follicular lymphoma to novel anti-CD19 CAR-T therapy with pseudo-progression and cytomegalovirus infection: A case report.

机构信息

Department of Hematology, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, 518052, China.

Shenzhen Cell Valley Biomedical Co., LTD, Shenzhen 518118, China.

出版信息

Int Immunopharmacol. 2024 Jun 15;134:112174. doi: 10.1016/j.intimp.2024.112174. Epub 2024 May 3.

Abstract

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. Most of these CARs were generated by lentivirus. With the exception of Yescarta and Tecartus, few patients with relapsed-/refractory- lymphoma have been treated clinically with a CARs using retroviral vector (RV). Here, we reported a relapsed/refractory grade 2 follicular lymphoma patient with multiple chemotherapy failures, and was treated with a novel CD19 CAR-T cell manufactured from a RV. After tumor burden was reduced with Obinutuzumab and Duvelisib, the patient was infused novel CD19 CAR-T cells at a dose of 3 × 10 cells/ kg. Then he experienced a rapid response and achieved almost complete remission by day 26. Only grade 2 CRS, bilateral submaxillary lymph node enlargement and cytomegalovirus (CMV) infection occurred without neurotoxicity, and the patient's condition improved after a series of symptomatic treatments. In addition, CAR copy number peaked at 532,350 copies/μg on day 15 and continued to expand for 5 months. This may be the first case report of RV preparation of novel CD19 CAR-T cells for direct treatment of recurrent follicular lymphoma. We will observe its long-term efficacy and conduct trials in more patients in the future.

摘要

CD19 导向的嵌合抗原受体 (CAR) T 细胞疗法已被证明可在难治性或复发性 B 细胞非霍奇金淋巴瘤患者中实现持久的缓解。这些 CAR 大多数是通过慢病毒产生的。除了 Yescarta 和 Tecartus,很少有复发性/难治性淋巴瘤患者接受过使用逆转录病毒载体 (RV) 的 CAR 临床治疗。在这里,我们报告了一例难治性/复发性 2 级滤泡性淋巴瘤患者,该患者经历了多次化疗失败,并接受了一种新型 CD19 CAR-T 细胞的治疗,该细胞由 RV 制造。在奥滨尤妥珠单抗和 Duvelisib 降低肿瘤负担后,以 3×10 个细胞/ kg 的剂量输注新型 CD19 CAR-T 细胞。然后,他迅速做出反应,在第 26 天达到几乎完全缓解。仅发生 2 级 CRS、双侧颌下淋巴结肿大和巨细胞病毒 (CMV) 感染,无神经毒性,经一系列对症治疗后病情改善。此外,CAR 拷贝数在第 15 天达到 532,350 拷贝/μg,并持续扩增 5 个月。这可能是首例使用 RV 制备新型 CD19 CAR-T 细胞直接治疗复发性滤泡性淋巴瘤的病例报告。我们将在未来观察其长期疗效并在更多患者中进行试验。

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