Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Int J Hematol. 2020 Feb;111(2):303-310. doi: 10.1007/s12185-019-02771-2. Epub 2019 Nov 11.
Tisagenlecleucel is an autologous T cell genetically modified ex vivo using a lentiviral vector encoding an anti-CD19 chimeric antigen receptor. Here, we present the efficacy and safety of tisagenlecleucel in a subgroup of Japanese patients with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (ALL). ELIANA was a single-arm, open-label, multicenter, phase 2 study. Patients were aged ≥ 3 years at screening to ≤ 21 years at the time of diagnosis, and had ≥ 5% lymphoblasts in bone marrow at screening. Primary endpoint was overall remission rate [ORR; complete remission (CR) + CR with incomplete blood recovery (CRi)] within 3 months after infusion. As of April 13, 2018, eight patients were enrolled and six had been infused. ORR was 66.7% (95% confidence interval 22.3-95.7); three patients achieved CR and one patient had CRi. All patients with CR/CRi were negative for minimal residual disease. One patient had CR/CRi lasting 19.5 + months. Cytokine release syndrome (CRS) and neurological events occurred in 83% and 17% of patients, respectively. CRS resolved with anti-cytokine therapy and supportive care. Two deaths occurred due to disease progression. No cases of cerebral edema were observed. Tisagenlecleucel produced high remission rates and durable responses offering a new treatment option for Japanese pediatric and young adults with r/r B-ALL.
tisagenlecleucel 是一种自体 T 细胞,通过慢病毒载体体外遗传修饰,表达抗 CD19 嵌合抗原受体。本研究旨在评估 tisagenlecleucel 在日本复发/难治性(r/r)B 细胞急性淋巴细胞白血病(ALL)患者中的疗效和安全性。ELIANA 是一项单臂、开放标签、多中心、Ⅱ期临床研究。患者筛选时年龄≥3 岁且≤21 岁,诊断时骨髓中至少有 5%原始淋母细胞。主要终点为输注后 3 个月内的总缓解率(ORR;完全缓解[CR]+CR 伴有不完全血液学恢复[CRi])。截至 2018 年 4 月 13 日,共纳入 8 例患者,其中 6 例已接受输注。ORR 为 66.7%(95%置信区间 22.3%-95.7%);3 例患者达 CR,1 例患者达 CRi。所有达 CR/CRi 的患者均为微小残留病阴性。1 例患者获得持续 19.5+个月的 CR/CRi。83%和 17%的患者分别出现细胞因子释放综合征(CRS)和神经事件。CRS 经抗细胞因子治疗和支持治疗得到缓解。2 例患者因疾病进展死亡。未观察到脑水肿病例。tisagenlecleucel 可产生高缓解率和持久应答,为日本 r/r B-ALL 儿童和青年患者提供了一种新的治疗选择。