Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Innovative Cellular Therapeutics Co., Ltd (formerly SiDanSai Biotechnology Co., Ltd), Shanghai, China.
Clin Cancer Res. 2017 Jul 1;23(13):3297-3306. doi: 10.1158/1078-0432.CCR-16-1799. Epub 2016 Dec 30.
Patients with relapsed/refractory acute lymphocytic leukemia (R/R ALL) have a poor prognosis. Chimeric antigen receptor-modified T cells against CD19 (CART19) have displayed anti-leukemia activities. However, data from systemic trials in Chinese patients are limited. T cells transduced with CD19-directed CAR lentiviral vectors were infused in patients with R/R ALL under fludarabine- and cyclophosphamide-based lymphodepletion. The postinfusion responses, toxicities, expansion, and persistence of CART19s in enrolled patients were observed and monitored. We enrolled 15 patients with R/R ALL. The median transduction efficiency of CART19s was 33%. cytotoxicity assays were conducted and showed prominent antileukemia activities with CART19s. The patients received CART19s infusion at doses of 1.1 × 10/kg to 9.8 × 10/kg. Twelve patients achieved complete remission 1 month after CART19s infusion. CART19s expanded and persisted in peripheral blood and bone marrow. At 150 days, the overall survival rate and leukemia-free survival rate were 65.5% and 37.8%, respectively. The cumulative incidence of relapse and the nonrelapse mortality rate were 54.5% and 7.7%, respectively. Four patients underwent subsequent haploidentical hematopoietic stem cell transplantation. In this trial, 10 patients experienced cytokine release syndrome (CRS). Grade 3 CRS developed in 40% of patients and was associated with a higher disease burden on day -1 and a higher number of previous relapses. This trial demonstrated potent antileukemia activities of CART19s in Chinese patients with R/R ALL. Disease relapse remained the main obstacle. However, patients with a high risk of relapse after CART19s might benefit from subsequent haploidentical hematopoietic stem cell transplantation. .
复发/难治性急性淋巴细胞白血病(R/R ALL)患者的预后较差。嵌合抗原受体修饰的针对 CD19(CART19)的 T 细胞显示出抗白血病活性。然而,来自中国患者的系统试验数据有限。在氟达拉滨和环磷酰胺为基础的淋巴耗竭下,将靶向 CD19 的 CAR 慢病毒载体转导的 T 细胞输注到 R/R ALL 患者中。观察和监测入组患者的输注后反应、毒性、CART19 的扩增和持续存在。我们入组了 15 例 R/R ALL 患者。CART19 的中位转导效率为 33%。进行了细胞毒性测定,结果显示 CART19 具有明显的抗白血病活性。患者接受了 1.1×10/kg 至 9.8×10/kg 的 CART19 输注剂量。12 例患者在 CART19 输注后 1 个月达到完全缓解。CART19 在外周血和骨髓中扩增和持续存在。在 150 天时,总生存率和无白血病生存率分别为 65.5%和 37.8%。复发累积发生率和非复发死亡率分别为 54.5%和 7.7%。4 例患者随后进行了半相合造血干细胞移植。在这项试验中,10 例患者发生细胞因子释放综合征(CRS)。40%的患者出现 3 级 CRS,与 -1 天疾病负担较高和既往复发次数较多相关。这项试验表明,CART19 在我国 R/R ALL 患者中具有强大的抗白血病活性。疾病复发仍然是主要障碍。然而,CART19 后复发风险较高的患者可能受益于随后的半相合造血干细胞移植。
N Engl J Med. 2014-10-16
Eur J Drug Metab Pharmacokinet. 2024-11
Pharmaceuticals (Basel). 2024-8-5
BMC Bioinformatics. 2024-5-20