Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia

作者：Shannon L. Maude, Noelle V. Frey, Pamela A. Shaw, Richard Aplenc, David M. Barrett, Nancy Bunin, Anne Chew, Vanessa Gonzalez, Zhaohui Zheng, Simon F. Lacey, Yolanda D. Mahnke, J. Joseph Melenhorst, Susan R. Rheingold, Angela Shen, David T. Teachey, Bruce L. Levine, Carl H. June, David L. Porter, Stephan A. Grupp · 发表于：New England Journal of Medicine · 年份：2014 · DOI：10.1056/nejmoa1407222 · 被引用次数：5472 · 研究领域：CAR-T cell therapy research、Acute Lymphoblastic Leukemia research、Virus-based gene therapy research

BACKGROUND: Relapsed acute lymphoblastic leukemia (ALL) is difficult to treat despite the availability of aggressive therapies. Chimeric antigen receptor-modified T cells targeting CD19 may overcome many limitations of conventional therapies and induce remission in patients with refractory disease. METHODS: We infused autologous T cells transduced with a CD19-directed chimeric antigen receptor (CTL019) lentiviral vector in patients with relapsed or refractory ALL at doses of 0.76×10(6) to 20.6×10(6) CTL019 cells per kilogram of body weight. Patients were monitored for a response, toxic effects, and the expansion and persistence of circulating CTL019 T cells. RESULTS: A total of 30 children and adults received CTL019. Complete remission was achieved in 27 patients (90%), including 2 patients with blinatumomab-refractory disease and 15 who had undergone stem-cell transplantation. CTL019 cells proliferated in vivo and were detectable in the blood, bone marrow, and cerebrospinal fluid of patients who had a response. Sustained remission was achieved with a 6-month event-free survival rate of 67% (95% confidence interval [CI], 51 to 88) and an overall survival rate of 78% (95% CI, 65 to 95). At 6 months, the probability that a patient would have persistence of CTL019 was 68% (95% CI, 50 to 92) and the probability that a patient would have relapse-free B-cell aplasia was 73% (95% CI, 57 to 94). All the patients had the cytokine-release syndrome. Severe cytokine-release syndrome, whi...