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[成熟B细胞肿瘤的嵌合抗原受体T细胞疗法——当前应用及实际考量]

[CAR T-cell therapy of mature B-cell neoplasms-Current use and practical considerations].

作者信息

Weber Theresa, Burchert Andreas, Subklewe Marion

机构信息

Universitätsklinikum Gießen und Marburg, Campus Marburg, Klinik für Hämatologie, Onkologie und Immunologie, Carreras Leukämie Centrum, Philipps-Universität Marburg, Baldingerstr., 35043, Marburg, Deutschland.

Medizinische Klinik und Poliklinik III, LMU Klinikum München, Marchioninistraße 25, 81377, München, Deutschland.

出版信息

Inn Med (Heidelb). 2025 Jul 11. doi: 10.1007/s00108-025-01953-x.

Abstract

Chimeric antigen receptor (CAR) T‑cell therapy represents a novel and highly effective immunotherapeutic approach in the treatment of malignant B‑cell neoplasms. Although the term B‑cell non-Hodgkin's lymphoma (B-NHL) is still frequently used in clinical practice, the pathologically accurate designation according to the 2022 World Health Organization (WHO) classification is mature B‑cell neoplasms. The use of CAR T‑cell therapy is currently approved for several subtypes of these diseases, including large B‑cell lymphoma (LBCL), primary mediastinal B‑cell lymphoma (PMBL), mantle cell lymphoma (MCL) and follicular lymphoma (FL). The approach involves the ex vivo genetic modification of autologous T‑cells to express a CAR targeting the B‑cell surface antigen CD19, enabling the selective elimination of malignant CD19-positive cells. Clinical studies and register data have demonstrated a high overall response rate, significant improvements in progression-free survival (PFS) and sometimes also in overall survival (OS) in the varíous lymphoma entities. Despite these promising results, CAR T‑cell therapy remains complex and requires careful selection of the indications and specialized management of associated toxicities. Typical, but mostly manageable side effects of CAR T‑cell therapy include cytokine release syndrome (CRS), neurotoxicity (immune effector cell-associated neurotoxicity syndrome, ICANS), hematotoxicity (immune effector cell-associated hematotoxicity, ICAHT) and protracted immune reconstitution leading to increased susceptibility to infections. Close collaboration between CAR T‑cell centers and institutions that are not CAR T‑cell certified or practices is essential for the success of treatment. This affects not only the appropriate indications and the selection of an optimal bridging therapy prior to CAR T‑cell infusion but also particularly the structured management of potential complications during the postoperative course, in particular infectious complications, which frequently occur in the outpatient setting. Early communication, clear responsibilities and standardized follow-up protocols are decisive to ensure safe and successful care after CAR T‑cell therapy.

摘要

嵌合抗原受体(CAR)T细胞疗法是治疗恶性B细胞肿瘤的一种新型高效免疫治疗方法。尽管临床实践中仍经常使用B细胞非霍奇金淋巴瘤(B-NHL)这一术语,但根据2022年世界卫生组织(WHO)分类,病理上准确的名称是成熟B细胞肿瘤。目前,CAR T细胞疗法已被批准用于这些疾病的几种亚型,包括大B细胞淋巴瘤(LBCL)、原发性纵隔B细胞淋巴瘤(PMBL)、套细胞淋巴瘤(MCL)和滤泡性淋巴瘤(FL)。该方法涉及对自体T细胞进行体外基因改造,以表达靶向B细胞表面抗原CD19的CAR,从而能够选择性清除恶性CD19阳性细胞。临床研究和登记数据表明,在各种淋巴瘤实体中,总体缓解率较高,无进展生存期(PFS)显著改善,有时总生存期(OS)也有所改善。尽管取得了这些令人鼓舞的结果,但CAR T细胞疗法仍然复杂,需要仔细选择适应症并对相关毒性进行专门管理。CAR T细胞疗法典型但大多可控的副作用包括细胞因子释放综合征(CRS)、神经毒性(免疫效应细胞相关神经毒性综合征,ICANS)、血液毒性(免疫效应细胞相关血液毒性,ICAHT)以及导致感染易感性增加的长期免疫重建。CAR T细胞中心与未获得CAR T细胞认证的机构或医疗机构之间的密切合作对于治疗成功至关重要。这不仅影响到合适的适应症以及CAR T细胞输注前最佳桥接治疗的选择,还特别影响到术后过程中潜在并发症的结构化管理,尤其是门诊环境中经常发生的感染性并发症。早期沟通、明确责任和标准化的随访方案对于确保CAR T细胞治疗后安全、成功的护理至关重要。

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