Etuvetidigene Autotemcel for the Treatment of Wiskott-Aldrich Syndrome.

Etuvetidigene autotemcel (etu-cel) is an autologous gene therapy consisting of hematopoietic stem and progenitor cells that have been transduced ex vivo with a lentiviral vector encoding WAS complementary DNA.

Etuvetidigene autotemcel（etu-cel）是一种自体基因疗法，由经过体外转导含有WAS互补DNA的慢病毒载体的造血干细胞和祖细胞组成。

Methods

We integrated data from two prospective open-label clinical studies (a phase 1-2 study with 8 participants and a phase 3 study with 10 participants) and an expanded-access program with 9 participants to evaluate the efficacy and safety of etu-cel in patients with Wiskott-Aldrich syndrome.

我们整合了两项前瞻性开放标签临床研究（一项有8名参与者的第一阶段至第二阶段研究和一项有10名参与者的第三阶段研究）以及一个有9名参与者的扩展访问计划的数据，以评估etu-cel在Wiskott-Aldrich综合征患者中的疗效和安全性。

The participants received a single intravenous infusion of etu-cel after rituximab administration and reduced-intensity conditioning.

参与者在利妥昔单抗给药和降低强度的预处理后接受了etu-cel的单次静脉输注。

The primary efficacy end points were overall survival, severe infections from 6 to 18 months after gene therapy, and moderate and severe bleeding events in the first 12 months after gene therapy.

主要疗效终点包括基因治疗后6至18个月的整体生存率、严重感染以及基因治疗后前12个月内的中度和重度出血事件。

Results for severe infections and moderate and severe bleeding are reported as the rate of events (number per person-year of observation), which was compared with the rate in the year before gene therapy.

严重感染和中度及重度出血的结果以事件率（每观察人年数）报告，与基因治疗前一年的率进行了比较。

Results

The median follow-up among the surviving participants was 5.7 years (range, 2.3 to 13.3), and the median age at the time of gene therapy was 2.6 years (range, 1.0 to 35.1).

存活的参与者的中位随访时间为5.7年（范围，2.3至13.3），基因治疗时的中位年龄为2.6岁（范围，1.0至35.1）。

Overall survivalat both 1 year and 5 years was 96%; one participant died.

1年和5年的整体生存率均为96%；有一名参与者死亡。

The most common adverse eventof grade 3 or higher was central venous catheter-related infection.

最常见的3级或更高级别的不良事件是与中心静脉导管相关的感染。

No evidence of insertional oncogenesis was observed.

未观察到插入性致癌的证据。

The rate of severe infections per person-year of observation decreased from 2.00 (95% confidence interval[CI], 1.50 to 2.61) in the year before gene therapy to 0.15 (95% CI, 0.04 to 0.39) in the period beyond 6 months up to 18 months after treatment.

严重感染的发生率从基因治疗前一年的每年人2.00次（95%置信区间[CI]，1.50至2.61）降低到治疗后6个月至18个月期间的每年人0.15次（95% CI，0.04至0.39）。

The rate of moderate or severe bleeding events per person-year of observation decreased from 2.00 (95% CI, 1.50 to 2.61) in the year before gene therapy to 0.80 (95% CI, 0.49 to 1.22) in the year after treatment.

中度或重度出血事件的发生率从基因治疗前一年的每年人2.00次（95% CI，1.50至2.61）降低到治疗后一年的每年人0.80次（95% CI，0.49至1.22）。

Conclusions

Our results show that the effects of etu-cel are consistent with a sustained clinical benefit in persons with Wiskott-Aldrich syndrome.

我们的研究结果显示，etu-cel的效果与Wiskott-Aldrich综合征患者持续的临床益处一致。

(Funded by Fondazione Telethon and others; TIGET-WAS and OTL-103-4 ClinicalTrials.gov numbers, NCT01515462 and NCT03837483, respectively.).

该项目由Fondazione Telethon和其他机构资助；TIGET-WAS和OTL-103-4的ClinicalTrials.gov编号分别为NCT01515462和NCT03837483。