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管理嵌合抗原受体 T 细胞疗法的毒性。

Managing the toxicities of CAR T-cell therapy.

机构信息

Department of Lymphoma and Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.

出版信息

Hematol Oncol. 2019 Jun;37 Suppl 1:48-52. doi: 10.1002/hon.2595.

Abstract

Chimeric antigen receptor (CAR) T-cell therapy has the potential to revolutionize the management of B-cell lymphomas and possibly other cancers. Two anti-CD19 CAR T-cell products, axicabtagene ciloleucel and tisagenlecleucel, have been approved for the management of relapsed/refractory large B-cell lymphoma after two lines of systemic therapy. Additional trials are ongoing to evaluate these and other CAR T products at earlier stages of the disease course as well as in other lymphomas. While the potential to induce durable remissions with a single CAR T-cell infusion even in patients who are chemorefractory has generated much enthusiasm in the field, practitioners need to familiarize themselves with the unique toxicities associated with these therapies. This review will discuss the grading and management of the two most common toxicities, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), observed acutely after this therapy. In addition, late toxicities including prolonged cytopenias and on-target off-tumor effects will be reviewed.

摘要

嵌合抗原受体 (CAR) T 细胞疗法有可能彻底改变 B 细胞淋巴瘤和其他癌症的治疗方式。两种抗 CD19 CAR T 细胞产品,axicabtagene ciloleucel 和 tisagenlecleucel,已被批准用于二线全身治疗后复发/难治性大 B 细胞淋巴瘤的治疗。正在进行额外的试验,以评估这些和其他 CAR T 产品在疾病早期阶段以及其他淋巴瘤中的疗效。虽然在化疗耐药的患者中,单次 CAR T 细胞输注就有可能诱导持久缓解,这在该领域引起了极大的关注,但临床医生需要熟悉这些治疗方法相关的独特毒性。本文将讨论这两种最常见的毒性反应(细胞因子释放综合征 [CRS] 和免疫效应细胞相关神经毒性综合征 [ICANS])的分级和管理,这些毒性反应在该疗法后急性发生。此外,还将回顾迟发性毒性反应,包括长期血细胞减少和靶肿瘤外效应。

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