一例利用持续性 CAR-T 细胞成功治疗 DLBCL 早期孤立性中枢神经系统复发的病例。

Blood cell therapy Pub Date : 2024-03-29 eCollection Date: 2024-05-25 DOI:10.31547/bct-2023-032
Ken Takigawa, Noriaki Kawano, Yasuo Mori, Takuji Yamauchi, Taro Tochigi, Kohta Miyawaki, Kyohei Mori, Masatoshi Shimo, Takashi Nakaike, Kiyoshi Yamashita, Koichi Mashiba, Ikuo Kikuchi, Kousuke Marutsuka, Koichi Ohshima, Koji Kato, Koichi Akashi
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引用次数: 0

摘要

继发性中枢神经系统(CNS)淋巴瘤通常需要穿透中枢神经系统的药物;然而,现有的药物效果有限,且疗效不佳。嵌合抗原受体T(CAR-T)细胞疗法(lisocabtagene maraleucel;liso-cel)已被用于治疗少数孤立的继发性中枢神经系统淋巴瘤病例。在此,我们报告了一例被诊断为弥漫大 B 细胞淋巴瘤(Ann Arbor 分级 IV;R-IPI,良好风险;中枢神经系统 IPI:中度风险)的 66 岁男性病例,他在接受了 6 个疗程的 R-CHOP 治疗后获得了完全缓解(CR)。三个月后,他出现上睑下垂和眼球运动障碍。全身 CT 和骨髓检查未发现淋巴瘤。虽然头颅增强 MRI 显示正常,但在脑脊液(CSF)中检测到具有原始淋巴瘤表型(CD19+CD79a+CD5-CD10-CD20-Igλ+)的 B 细胞数量增加(51/μL),表明有孤立的中枢神经系统复发。七个大剂量甲氨蝶呤疗程导致部分反应。随后,患者接受了CAR-T细胞治疗,不良反应尚可耐受--使用托珠单抗治疗细胞因子释放综合征,未出现免疫效应细胞相关神经毒性综合征,使用粒细胞集落刺激因子和艾曲波帕治疗骨髓衰竭。序贯流式细胞术显示,CAR-T细胞的峰值很高,外周血中存在残余的CAR-T细胞,这表明CAR-T细胞对中枢神经系统淋巴瘤进行了免疫监视。这种治疗方法使患者第二次获得 CR。该病例首次在临床实践中验证了CAR-T细胞疗法治疗孤立性继发性中枢神经系统淋巴瘤的有效性和安全性。今后,积累 CAR-T 细胞疗法疗效和安全性方面的证据至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

A case of successful CAR-T cell therapy for early isolated CNS recurrence of DLBCL with persistent CAR-T cells.

A case of successful CAR-T cell therapy for early isolated CNS recurrence of DLBCL with persistent CAR-T cells.

A case of successful CAR-T cell therapy for early isolated CNS recurrence of DLBCL with persistent CAR-T cells.

Secondary central nervous system (CNS) lymphomas typically require CNS-penetrating drugs; however, the available agents are limited with temporary effects and poor outcomes. Chimeric antigen receptor T (CAR-T) cell therapy (lisocabtagene maraleucel; liso-cel) has been used to treat a few cases of isolated secondary CNS lymphoma. Herein, we report the case of a 66-year-old male diagnosed with diffuse large B-cell lymphoma (Ann Arbor grade IV; R-IPI, good risk; CNS IPI: Intermediate risk) who achieved complete remission (CR) after six courses of R-CHOP therapy. Three months later, he presented with ptosis and eye movement disorder. Systemic CT and bone marrow examination revealed no lymphoma. Although cranial-enhanced MRI showed normal findings, an increased number of B-cells (51/μL) with the original lymphoma phenotype (CD19+CD79a+CD5-CD10-CD20-Igλ+) was detected in cerebrospinal fluid (CSF), indicating an isolated CNS relapse. Seven high-dose methotrexate courses led to partial response. Subsequently, the patient received CAR-T cell therapy with tolerable adverse events - cytokine release syndrome treated with tocilizumab, no immune effector cell-associated neurotoxicity syndrome, and bone marrow failure treated with granulocyte-colony stimulating factor and eltrombopag. Sequential flow cytometry revealed a high peak of CAR-T cells and the presence of residual CAR-T cells in the peripheral blood, indicating immune surveillance of CNS lymphoma by CAR-T cells. This treatment led to a second CR. This case is the first to validate the efficacy and safety of CAR-T cell therapy for isolated secondary CNS lymphoma in clinical practice. Future accumulation of evidence on the efficacy and safety of CAR-T cell therapy is essential.

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