Chimeric Antigen Receptor T Cells forSustained Remissions in Leukemia 应用CAR-T技术后的白血病患者病情得到持续缓解 Abstract: BACKGROUND: Relapsed acutelymphoblastic leukemia (ALL) is difficult to treat despite the availability ofaggressive therapies. Chimeric antigen receptor–modified T cells targeting CD19may overcome many limitations of conventional therapies and induce remission inpatients with refractory disease. 背景: 复发急性淋巴细胞白血病(ALL)尽管积极的治疗也是难以治愈的,靶向CD19嵌合抗原受体修饰的T细胞可以克服传统疗法的诸多限制和诱导缓解难治性疾病的患者。 METHODS: We infused autologousT cells transduced with a CD19-directed chimeric antigen receptor (CTL019) lentiviralvector in patients with relapsed or refractory ALL at doses of 0.76×106 to20.6×106 CTL019 cells per kilogram of body weight. Patients were monitored fora response, toxic effects, and the expansion and persistence of circulatingCTL019 T cells. 方法: 我们向患有复发难治性ALL患者体内注入转导了每千克体重的剂量为0.76×106 至20.6×106 的CD19导向嵌合抗原受体(CTL019)的慢病毒载体,我们监测患者的反应,毒性作用,循环CTL019 T细胞的扩张性和持久性。 RESULTS: A total of 30children and adults received CTL019. Complete remission was achieved in 27patients (90%), including 2 patients with blinatumomab-refractory disease and15 who had undergone stem-cell transplantation. CTL019 cells proliferated invivo and were detectable in the blood, bone marrow, and cerebrospinalf luid ofpatients who had a response. Sustained remission was achieved with a 6-monthevent-free survival rate of 67% (95% confidence interval [CI], 51 to 88) and anoverall survival rate of 78% (95% CI, 65 to 95). At 6 months, the probabilitythat a patient would have persistence of CTL019 was 68% (95% CI, 50 to 92) andthe 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. Severecytokine-release syndrome, which developed in 27% of the patients, wasassociated with a higher disease burden before infusion and was effectivelytreated with the anti–interleukin-6 receptor antibody tocilizumab. 结果: 共有30名儿童和成人注射了CTL019。病情得到完全缓解的有27例(90%),其中包括2例患有blinatumomab难治性疾病和15 例经历了干细胞移植的患者。 CTL019细胞在体内增殖,并且在起反应的患者血液,骨髓和脑脊髓液是可检测到的。病情得以持续缓解是以67%的6个月无事件生存率(95%置信区间[CI],51〜88)和78%的总生存率(95%CI,65〜95)来实现的。在这6个月,一个患者的CTL019的持久性的概率为68%(95%CI,50至92),具有无复发B细胞发育不全的概率为73%(95%CI,57至94)。所有患者都患有细胞因子释放综合征。27%的患者表明严重的细胞因子释放综合征与患者注入慢病毒载体前的较高疾病负担有关,这种疾病被抗白介素-6受体抗体的托珠单抗有效地治疗。 CONCLUSIONS: Chimeric antigen receptor–modified T-cell therapyagainst CD19 was effective in treating relapsed and refractory ALL. CTL019 wasassociated with a high remission rate, even among patients for whom stem-cell transplantationhad failed, and durable remissions up to 24 months were observed. 结论: 靶向CD19嵌合抗原受体修饰的T细胞疗法是治疗复发和难治性ALL的患者的有效方法。CTL019具有很高缓解率,即使是干细胞移植失败的患者,在长达24个月的观察治疗中也达到了持续的缓解。
|