成熟b细胞肿瘤的CAR - t细胞治疗——目前的使用和实际考虑。

Theresa Weber, Andreas Burchert, Marion Subklewe
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引用次数: 0

摘要

嵌合抗原受体(CAR) T细胞疗法是治疗恶性B细胞肿瘤的一种新颖高效的免疫治疗方法。尽管B细胞非霍奇金淋巴瘤(B- nhl)这一术语在临床实践中仍然经常使用,但根据2022年世界卫生组织(WHO)的分类,病理学上准确的名称是成熟B细胞肿瘤。CAR - T细胞疗法目前已被批准用于治疗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细胞进行体外遗传修饰,以表达靶向B细胞表面抗原CD19的CAR,从而能够选择性地消除恶性CD19阳性细胞。临床研究和登记数据表明,在varíous淋巴瘤实体中,总体缓解率高,无进展生存期(PFS)显着改善,有时也显着改善总生存期(OS)。尽管有这些有希望的结果,CAR - T细胞疗法仍然很复杂,需要仔细选择适应症和专门管理相关的毒性。CAR - T细胞治疗的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)和导致感染易感性增加的长期免疫重建。CAR - T细胞中心和非CAR - T细胞认证或实践机构之间的密切合作对于治疗的成功至关重要。这不仅影响到CAR - T细胞输注前适当的适应症和最佳桥接治疗的选择,而且还影响到术后过程中潜在并发症的结构化管理,特别是门诊经常发生的感染性并发症。早期沟通、明确的责任和标准化的随访方案是确保CAR - T细胞治疗后安全和成功护理的决定性因素。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
[CAR T-cell therapy of mature B-cell neoplasms-Current use and practical considerations].

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.

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