Effective response and delayed toxicities of refractory advanced diffuse large B-cell lymphoma treated by CD20-directed chimeric antigen receptor-modified T cells
Effective response and delayed toxicities of refractory advanced diffuse large B-cell lymphoma treated by CD20-directed chimeric antigen receptor-modified T cells
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CD20 定向嵌合抗原受体修饰 T 细胞治疗难治性晚期弥漫性大 B 细胞淋巴瘤的有效反应和延迟毒性。
DOI：
10.1016/j.clim.2014.10.002
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发表时间：
2014-12-01
影响因子：
8.6
通讯作者：
Han, Wei-dong
中科院分区：
文献类型：
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作者：
Wang, Yao;Zhang, Wen-ying;Han, Wei-dong
我们在化疗难治性晚期弥漫性大B细胞淋巴瘤(DLBCL)患者中进行了一项试验，测试CD20特异性CAR与CD137和CD3 Zeta部分结合。共有7名患者入选。两名没有肿块的患者中，一名患者仅通过细胞输注获得了持续14个月的持久完全缓解，另一名患者的肿瘤消退时间为6个月。5例肿瘤负担较大的患者中有4例可评估临床疗效，其中3例获得3-6个月的肿瘤消退。与细胞输注相关的延迟毒性与肿瘤负荷和肿瘤部位直接相关，主要包括细胞因子释放症状、肿瘤溶解症状、消化道大出血和结外病变周围的侵袭性肺内炎症。这些结果表明，抗CD20CART细胞联合去瘤预适应方案治疗晚期DLBCL可延长肿瘤消退时间。这项研究在www.Clinicaltrials.gov上注册为NCT01735604。(C)2014 Elsevier Inc.保留所有权利。
We conducted a trial testing a CD20-specific CAR coupled with CD137 and the CD3 zeta moiety in patients with chemotherapy refractory advanced diffuse large B cell lymphomas (DLBCL). Seven patients were enrolled. One of the two patients with no bulky tumor obtained a 14-month durable and ongoing complete remission by cell infusion only, and another attained a 6-month tumor regression. Four of five patients with bulky tumor burden were evaluable for clinical efficacy, three of which attained 3- to 6-month tumor regression. Delayed toxicities related to cell infusion are directly correlated to tumor burden and tumor-harboring sites, and mainly included cytokine release symptoms, tumor lysis symptoms, massive hemorrhage of the alimentary tract and aggressive intrapulmonary inflammation surrounding extranodal lesions. These results show firstly that anti-CD20 CART cells can cause prolonged tumor regression in combination with debulking conditioning regimens for advanced DLBCL. This study is registered at www.clinicaltrials.gov as NCT01735604. (C) 2014 Elsevier Inc. All rights reserved.