Riedell Peter A, Bishop Michael R
Hematopoietic Cellular Therapy Program, Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA.
Section of Hematology/Oncology, Department of Medicine, The University of Chicago, 5841 S. Maryland Ave., MC 2115, Chicago, IL 60637, USA.
Ther Adv Hematol. 2020 Jan 29;11:2040620720902899. doi: 10.1177/2040620720902899. eCollection 2020.
Aggressive large B-cell lymphomas represent a diverse population of diseases that are typically treated with anti-CD20 based immunochemotherapy. While this treatment is effective for a large proportion of patients, those that become refractory to induction therapy or experience disease relapse suffer an inferior overall prognosis, and novel treatment options are needed. Adoptive T-cell immunotherapy in the form of chimeric antigen receptor (CAR) T-cell therapy is one of the most revolutionary breakthroughs in the past several decades for the treatment of relapsed/refractory aggressive large B-cell lymphomas. Based on data from the pivotal ZUMA-1 study, axicabtagene ciloleucel (axi-cel) became the first-in-class anti-CD19 directed CAR T-cell therapy approved for patients with diffuse large B-cell lymphoma and other aggressive B-cell lymphoma variants. In this review, we provide an overview of CAR T-cell therapy, including its biology, manufacturing, and treatment course. In addition, we highlight the available efficacy data, review pertinent safety concerns, including cytokine release syndrome and neurologic toxicity, as well as provide an overview of emerging therapeutic strategies in the cellular therapy arena.
侵袭性大B细胞淋巴瘤是一类多样的疾病,通常采用基于抗CD20的免疫化疗进行治疗。虽然这种治疗方法对大部分患者有效,但那些对诱导治疗无效或经历疾病复发的患者总体预后较差,因此需要新的治疗选择。嵌合抗原受体(CAR)T细胞疗法形式的过继性T细胞免疫疗法是过去几十年来治疗复发/难治性侵袭性大B细胞淋巴瘤最具革命性的突破之一。基于关键的ZUMA-1研究数据,阿基仑赛注射液(axi-cel)成为首个获批用于弥漫性大B细胞淋巴瘤和其他侵袭性B细胞淋巴瘤变体患者的抗CD19导向CAR T细胞疗法。在本综述中,我们概述了CAR T细胞疗法,包括其生物学特性、制备过程和治疗疗程。此外,我们强调了现有的疗效数据,回顾了相关的安全问题,包括细胞因子释放综合征和神经毒性,并概述了细胞治疗领域新兴的治疗策略。