Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia.
Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia.
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DOI：
10.1056/nejmoa1709919
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发表时间：
2018-02-01
期刊：
影响因子：
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通讯作者：
Sadelain M
中科院分区：
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作者：
Park JH;Rivière I;Gonen M;Wang X;Sénéchal B;Curran KJ;Sauter C;Wang Y;Santomasso B;Mead E;Roshal M;Maslak P;Davila M;Brentjens RJ;Sadelain M
CD 19特异性嵌合抗原受体（CAR）T细胞在复发性B细胞急性淋巴细胞白血病（ALL）患者中诱导高初始应答率，并在一个亚组患者中诱导长期缓解。我们在Memorial Sloan Kettering Cancer Center（MSKCC）进行了一项1期试验，涉及复发性B细胞ALL成人患者，他们接受了表达19- 28 z CAR的自体T细胞输注。评估了安全性和长期结局，以及它们与人口统计学、临床和疾病特征的相关性。共有53名成年人接受了在MSKCC生产的19- 28 z CAR T细胞。输注后，53例患者中有14例发生重度细胞因子释放综合征（26%; 95%置信区间[CI]，15 - 40）; 1例患者死亡。在83%的患者中观察到完全缓解。中位随访时间为29个月（范围：1 - 65），中位无事件生存期为6.1个月（95% CI，5.0 - 11.5），中位总生存期为12.9个月（95% CI，8.7 - 23.4）。治疗前疾病负荷较低（骨髓原始细胞<5%）的患者缓解持续时间和生存率显著延长，中位无事件生存期为10.6个月（95%CI，5.9至未达到），中位总生存期为20.1个月（95%CI，8.7至未达到）。与疾病负担低的患者相比，疾病负担高的患者（≥5%骨髓原始细胞或髓外疾病）细胞因子释放综合征和神经毒性事件的发生率更高，长期生存期更短。整个队列的中位总生存期为12.9个月。在低疾病负担的患者中，中位总生存期为20.1个月，并且在19- 28 z CAR T细胞输注后，细胞因子释放综合征和神经毒性事件的发生率明显低于在高疾病负担的患者中观察到的发生率。（由英联邦癌症研究基金会和其他机构资助; ClinicalTrials.gov编号，。
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. 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. 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 events and shorter long-term survival than did patients with a low disease burden. In the entire cohort, the median overall survival was 12.9 months. Among patients with a low disease burden, the median overall survival was 20.1 months and was accompanied by a markedly lower incidence of the cytokine release syndrome and neurotoxic events after 19–28z CAR T-cell infusion than was observed among patients with a higher disease burden. (Funded by the Commonwealth Foundation for Cancer Research and others; ClinicalTrials.gov number, .)