Sharma P, King G T, Shinde S S, Purev E, Jimeno A
Division of Hematology, Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA.
Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA.
Drugs Today (Barc). 2018 Mar;54(3):187-198. doi: 10.1358/dot.2018.54.3.2776625.
B-cell non-Hodgkin's lymphomas are the most common hematological malignancies, which despite improvements in chemo-immunotherapy, carry a uniformly poor prognosis in the relapsed/refractory setting. CD19 is an antigen expressed on the surface of most malignancies arising from the B cells, and adoptive transfer of anti-CD19 chimeric antigen receptor (CAR)-expressing T cells has been shown to be effective in treating these B-cell malignancies. Axicabtagene ciloleucel (axi-cel, KTE-C19) is an autologous anti-CD19 CAR T-cell therapy which has shown high overall response rates and a manageable safety profile in patients with relapsed or refractory B-cell malignancies who lack effective and curative treatment options. Axi-cel is currently approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy including diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma and DLBCL arising from follicular lymphoma, and is also being evaluated in other B-cell malignancies in ongoing clinical trials. In this review we will discuss the mechanism of action of axi-cel, clinical trials leading to its FDA approval, ongoing clinical trials and its potential adverse effects, and will speculate on the future directions of axi-cel and CAR T-cell therapy in general.
B细胞非霍奇金淋巴瘤是最常见的血液系统恶性肿瘤,尽管化疗免疫疗法有所改进,但在复发/难治性情况下预后普遍较差。CD19是一种在大多数B细胞来源的恶性肿瘤表面表达的抗原,过继转移表达抗CD19嵌合抗原受体(CAR)的T细胞已被证明对治疗这些B细胞恶性肿瘤有效。阿基仑赛注射液(axi-cel,KTE-C19)是一种自体抗CD19 CAR T细胞疗法,在缺乏有效治愈性治疗方案的复发或难治性B细胞恶性肿瘤患者中显示出高总体缓解率和可控的安全性。阿基仑赛注射液目前已获美国食品药品监督管理局(FDA)批准,用于治疗接受过两种或更多线全身治疗后的复发或难治性大B细胞淋巴瘤成年患者,包括弥漫性大B细胞淋巴瘤(DLBCL)、原发性纵隔大B细胞淋巴瘤、高级别B细胞淋巴瘤以及滤泡性淋巴瘤转化的DLBCL,并且正在其他B细胞恶性肿瘤的正在进行的临床试验中进行评估。在本综述中,我们将讨论阿基仑赛注射液的作用机制、导致其获得FDA批准的临床试验、正在进行的临床试验及其潜在不良反应,并将总体推测阿基仑赛注射液和CAR T细胞疗法的未来发展方向。
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