Department of Hematology, Graduate School of Medicine, Hokkaido University Faculty of Medicine, Sapporo, Japan.
Department of Hematology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan.
Int J Clin Oncol. 2020 Sep;25(9):1736-1743. doi: 10.1007/s10147-020-01699-6. Epub 2020 May 24.
Tisagenlecleucel demonstrated a high rate of durable response in adult patients with relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) in the pivotal global phase 2 JULIET study. Here, we report the efficacy and safety of tisagenlecleucel in the Japanese subgroup.
JULIET (NCT02445248) is a single-arm, open-label, multicenter, phase 2 study involving adult patients with r/r DLBCL who either relapsed after or were ineligible for autologous stem cell transplant. Primary endpoint was best overall response rate (ORR; complete response [CR] + partial response [PR]) as judged by an independent review committee.
In Japan, of 17 patients enrolled, 9 were infused with tisagenlecleucel and completed ≥ 3 months of follow-up. Best ORR was 77.8% (7/9; 95% confidence interval, 40.0-97.2), with 5 patients (55.6%) in CR and 2 (22.2%) in PR. Cytokine release syndrome (CRS) occurred in 6 patients (66.7%), with grade 3 CRS in 2 patients (Penn grading scale). Two patients received tocilizumab. Two deaths (22.2%) occurred more than 30 days after tisagenlecleucel infusion due to disease progression, neither of which were related to tisagenlecleucel.
Tisagenlecleucel showed a high best ORR with a manageable safety profile, thus offering a new treatment option in selected Japanese patients with r/r DLBCL.
Tisagenlecleucel 在关键性全球 2 期 JULIET 研究中显示出对复发/难治性（r/r）弥漫性大 B 细胞淋巴瘤（DLBCL）成年患者的持久应答率较高。在此，我们报告 tisagenlecleucel 在日本亚组中的疗效和安全性。
JULIET（NCT02445248）是一项单臂、开放标签、多中心、2 期研究，纳入 r/r DLBCL 成年患者，这些患者在自体干细胞移植后复发或不符合自体干细胞移植条件。主要终点为独立审查委员会评估的最佳总体缓解率（ORR；完全缓解[CR]+部分缓解[PR]）。
在日本，17 名入组患者中，有 9 名接受了 tisagenlecleucel 输注，并完成了≥3 个月的随访。最佳 ORR 为 77.8%（7/9；95%置信区间，40.0-97.2），5 名患者（55.6%）达到 CR，2 名患者（22.2%）达到 PR。6 名患者（66.7%）发生细胞因子释放综合征（CRS），其中 2 名患者（Penn 分级量表）发生 3 级 CRS。2 名患者接受了托珠单抗治疗。2 名患者（22.2%）在 tisagenlecleucel 输注后 30 天以上死亡，均与 tisagenlecleucel 无关，均由于疾病进展所致。
Tisagenlecleucel 在日本 r/r DLBCL 患者中显示出高最佳 ORR，安全性可管理，为其提供了一种新的治疗选择。
