Chavez Julio C, Bachmeier Christina, Kharfan-Dabaja Mohamed A
Department of Malignant Hematology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA.
Department of Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, FL, USA.
Ther Adv Hematol. 2019 Apr 15;10:2040620719841581. doi: 10.1177/2040620719841581. eCollection 2019.
Adoptive cellular immunotherapy with chimeric antigen receptor (CAR) T cell has changed the treatment landscape of B-cell non-Hodgkin's lymphoma (NHL), especially for aggressive B-cell lymphomas. Single-center and multicenter clinical trials with anti-CD19 CAR T-cell therapy have shown great activity and long-term remissions in poor-risk diffuse large B-cell lymphoma (DLBCL) when no other effective treatment options are available. Two CAR T-cell products [axicabtagene ciloleucel (axi-cel) and tisagenlecleucel] have obtained US Food and Drug Administration approval for the treatment of refractory DLBCL after two lines of therapy. A third product, liso-cel, is currently being evaluated in clinical trials and preliminary results appear very promising. CAR T-cell-related toxicity with cytokine-release syndrome and neurotoxicity remain important potential complications of this therapy. Here, we review the s biology, structure, clinical trial results and toxicity of two commercially approved CAR T-cell products and others currently being studied in multicenter clinical trials in B-cell NHLs.
嵌合抗原受体(CAR)T细胞的过继性细胞免疫疗法改变了B细胞非霍奇金淋巴瘤(NHL)的治疗格局,尤其是侵袭性B细胞淋巴瘤。抗CD19 CAR T细胞疗法的单中心和多中心临床试验表明,在没有其他有效治疗选择的情况下,其对预后不良的弥漫性大B细胞淋巴瘤(DLBCL)具有显著疗效和长期缓解作用。两种CAR T细胞产品[阿基仑赛(axi-cel)和替雷利珠单抗(tisagenlecleucel)]已获得美国食品药品监督管理局批准,用于治疗经过两线治疗后的难治性DLBCL。第三种产品,来苏单抗(liso-cel),目前正在临床试验中进行评估,初步结果看起来非常有前景。CAR T细胞相关的毒性,如细胞因子释放综合征和神经毒性,仍然是这种疗法的重要潜在并发症。在此,我们综述了两种已获商业批准的CAR T细胞产品以及目前正在B细胞NHL多中心临床试验中研究的其他产品的生物学、结构、临床试验结果和毒性。