Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia

作者：Jae H. Park, Isabelle Rivière, Mithat Gönen, Xiuyan Wang, Brigitte Sénéchal, Kevin J. Curran, Craig S. Sauter, Yongzeng Wang, Bianca Santomasso, Elena Mead, Mikhail Roshal, P. Maslak, Marco L. Davila, Renier J. Brentjens, Michel Sadelain · 发表于：New England Journal of Medicine · 年份：2018 · DOI：10.1056/nejmoa1709919 · 被引用次数：2726 · 研究领域：CAR-T cell therapy research、Acute Lymphoblastic Leukemia research、Lymphoma Diagnosis and Treatment

BACKGROUND: CD19-specific chimeric antigen receptor (CAR) T cells induce high rates of initial response among patients with relapsed B-cell acute lymphoblastic leukemia (ALL) and long-term remissions in a subgroup of patients. METHODS: We conducted a phase 1 trial involving adults with relapsed B-cell ALL who received an infusion of autologous T cells expressing the 19-28z CAR at the Memorial Sloan Kettering Cancer Center (MSKCC). Safety and long-term outcomes were assessed, as were their associations with demographic, clinical, and disease characteristics. RESULTS: A total of 53 adults received 19-28z CAR T cells that were manufactured at MSKCC. After infusion, severe cytokine release syndrome occurred in 14 of 53 patients (26%; 95% confidence interval [CI], 15 to 40); 1 patient died. Complete remission was observed in 83% of the patients. At a median follow-up of 29 months (range, 1 to 65), the median event-free survival was 6.1 months (95% CI, 5.0 to 11.5), and the median overall survival was 12.9 months (95% CI, 8.7 to 23.4). Patients with a low disease burden (<5% bone marrow blasts) before treatment had markedly enhanced remission duration and survival, with a median event-free survival of 10.6 months (95% CI, 5.9 to not reached) and a median overall survival of 20.1 months (95% CI, 8.7 to not reached). Patients with a higher burden of disease (≥5% bone marrow blasts or extramedullary disease) had a greater incidence of the cytokine release syndrome and neurotoxic event...