Long-term efficacy and safety results of betibeglogene autotemcel gene therapy for transfusion-dependent β-thalassemia.

Sixty-three participants with TDT (median age, 17 years [range, 4-35]) received beti-cel in phase 1/2 (n = 22) or phase 3 (n = 41) studies and enrolled in the long-term follow-up LTF-303 study (median follow-up, 5.9 years [range, 2.9-10.1]).

63名患有TDT的参与者（中位年龄17岁[范围4-35岁]）在1/2期（n=22）或3期（n=41）研究中接受了beti-cel治疗，并参与了长期随访LTF-303研究（中位随访时间5.9年[范围2.9-10.1年]）。

Manufacturing refinements in phase 3 increased transduction efficiency, resulting in higher drug product vector copy number and HbAT87Q levels, which translated into higher Hb and transfusion independence (TI) rates than in phase 1/2.

在III期临床试验中，制造工艺的改进提高了转导效率，导致药物产品载体拷贝数和HbAT87Q水平的提高，这转化为比I/II期更高的血红蛋白水平和输血独立性(TI)率。

TI was achieved by 15 of 22 (68.2%) phase 1/2 participants (median weighted average Hb during TI, 10.2 g/dL) and 37 of 41 (90.2%) of phase 3 participants (median, 11.2 g/dL), and was sustained through last follow-up.

在I/II期的22名参与者中有15名（68.2%）实现了TI（TI期间的中位加权平均血红蛋白为10.2 g/dL），而在III期的41名参与者中有37名（90.2%）实现了TI（中位数为11.2 g/dL），并且在最后一次随访时仍然维持TI。

Treatment efficacy was similar across ages and TDT genotypes.

治疗效果在不同年龄和TDT基因型之间相似。

Among participants achieving TI, 38 of 52 (73%) had discontinued iron chelation at last follow-up, with no increase in liver iron concentration.

在达到TI的参与者中，52人中有38人（73%）在最后随访时已停止铁螯合治疗，且肝铁浓度没有增加。

Markers of ineffective erythropoiesis, including serum transferrin receptor and erythropoietin, improved with restoration of iron homeostasis.

无效红细胞生成的标志物，包括血清转铁蛋白受体和促红细胞生成素，在铁稳态恢复后有所改善。

Health-related quality-of-life assessment scores showed durable improvements.

健康相关生活质量评估得分显示出持久的改善。

No malignancies, insertional oncogenesis, or vector-derived replication-competent lentivirus were reported.

未报告恶性肿瘤、插入性致癌作用或载体衍生的复制型慢病毒。

These findings establish beti-cel as a durable, 1-time therapy that achieves TI, restores iron balance, and improves quality of life, offering a potentially curative treatment option for people with TDT.

这些发现确立了beti-cel作为一次性的持久治疗，能够实现输血独立性，恢复铁平衡，并改善生活质量，为患有TDT的人们提供了一种潜在的治愈性治疗选择。

This trial was registered at www.clinicaltrials.gov as NCT02633943.

该试验已在www.clinicaltrials.gov上注册，注册号为NCT02633943。