Chemotherapy-Refractory Diffuse Large B-Cell Lymphoma and Indolent B-Cell Malignancies Can Be Effectively Treated With Autologous T Cells Expressing an Anti-CD19 Chimeric Antigen Receptor
Chemotherapy-Refractory Diffuse Large B-Cell Lymphoma and Indolent B-Cell Malignancies Can Be Effectively Treated With Autologous T Cells Expressing an Anti-CD19 Chimeric Antigen Receptor
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DOI：
10.1200/jco.2014.56.2025
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发表时间：
2015-02-20
影响因子：
45.3
通讯作者：
Rosenberg, Steven A.
中科院分区：
文献类型：
--
作者：
Kochenderfer, James N.;Dudley, Mark E.;Rosenberg, Steven A.
目的通过基因修饰T细胞，使其表达抗CD 19嵌合抗原受体（CAR）。我们评估了自体抗CD 19 CAR T细胞对晚期CD 19（+）B细胞恶性肿瘤患者的安全性和有效性。9例患者患有弥漫性大B细胞淋巴瘤（DLBCL），2例患有惰性淋巴瘤，4例患有慢性淋巴细胞白血病。患者接受了环磷酰胺和氟达拉滨的预处理化疗方案，然后单次输注抗CD 19 CAR T cells.ResultsOf 15例患者中，8例达到完全缓解（CR），4例达到部分缓解，1例淋巴瘤稳定，2例无法评估反应。7例可评价的化疗难治性DLBCL患者中有4例获得CR;这4例CR中有3例正在进行中，持续时间范围为9 - 22个月。一些患者在输注抗CD 19 CAR T细胞后发生急性毒性，包括发热、低血压、谵妄和其他神经系统毒性;这些毒性在细胞输注后3周内消退。1例患者在细胞输注后16天突然死亡，原因不明。在患者血液中检测到峰值水平的CAR T细胞，范围为9至777个CAR阳性T细胞/L。结论这是我们所知的抗CD 19 CAR T细胞成功治疗DLBCL的第一份报告。这些结果证明了用抗CD 19 CAR T细胞治疗化疗难治性B细胞恶性肿瘤的可行性和有效性。获得的大量缓解为进一步发展这种方法提供了强有力的支持。(C)2014年美国临床肿瘤学会
PurposeT cells can be genetically modified to express an anti-CD19 chimeric antigen receptor (CAR). We assessed the safety and efficacy of administering autologous anti-CD19 CAR T cells to patients with advanced CD19(+) B-cell malignancies.Patients and MethodsWe treated 15 patients with advanced B-cell malignancies. Nine patients had diffuse large B-cell lymphoma (DLBCL), two had indolent lymphomas, and four had chronic lymphocytic leukemia. Patients received a conditioning chemotherapy regimen of cyclophosphamide and fludarabine followed by a single infusion of anti-CD19 CAR T cells.ResultsOf 15 patients, eight achieved complete remissions (CRs), four achieved partial remissions, one had stable lymphoma, and two were not evaluable for response. CRs were obtained by four of seven evaluable patients with chemotherapy-refractory DLBCL; three of these four CRs are ongoing, with durations ranging from 9 to 22 months. Acute toxicities including fever, hypotension, delirium, and other neurologic toxicities occurred in some patients after infusion of anti-CD19 CAR T cells; these toxicities resolved within 3 weeks after cell infusion. One patient died suddenly as a result of an unknown cause 16 days after cell infusion. CAR T cells were detected in the blood of patients at peak levels, ranging from nine to 777 CAR-positive T cells/L.ConclusionThis is the first report to our knowledge of successful treatment of DLBCL with anti-CD19 CAR T cells. These results demonstrate the feasibility and effectiveness of treating chemotherapy-refractory B-cell malignancies with anti-CD19 CAR T cells. The numerous remissions obtained provide strong support for further development of this approach. (C) 2014 by American Society of Clinical Oncology