The phase III study was designed to compare event-free survival (EFS) after treosulfan-based conditioning with a widely applied reduced-intensity conditioning (RIC) busulfan regimen in older or comorbid patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic cell transplantation (HCT). A previously reported confirmatory interim analysis of the randomized clinical study including 476 patients demonstrated statistically significant noninferiority for treosulfan with clinically meaningful improvement in EFS. Here, the final study results and pre-specified subgroup analyses of all 570 randomized patients with completed longer-term follow-up are presented. Patients presenting HCT-specific comorbidity index >2 or aged ≥50 years were randomly assigned (1:1) to intravenous (IV) fludarabine with either treosulfan (30 g/m² IV) or busulfan (6.4 mg/kg IV) after stratification by disease risk group, donor type, and participating institution. The primary endpoint was EFS with disease recurrence, graft failure, or death from any cause as events. EFS of patients (median age 60 years) was superior after treosulfan compared to RIC busulfan: 36-months-EFS rate 59.5% (95% CI, 52.2–66.1) vs. 49.7% (95% CI, 43.3–55.7) with a hazard ratio (HR) of 0.64 (95% CI, 0.49–0.84), p = 0.0006. Likewise, overall survival (OS) with treosulfan was superior compared to busulfan: 36-month-OS rate 66.8% vs. 56.3%; HR 0.64 (95% CI, 0.48–0.87), p = 0.0037. Post hoc analyses revealed that these differences were consistent with the confirmatory interim analysis, and thereby the treosulfan regimen appears particularly suitable for older AML and MDS patients.

中文翻译：

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与低强度白消安相比，曲硫丹可改善老年急性髓细胞白血病和骨髓增生异常综合征患者的异基因造血细胞移植结果：一项前瞻性随机试验的最终分析

III 期研究旨在比较老年或合并急性髓性白血病 (AML) 或骨髓增生异常综合征 (MDS) 患者在基于三硫丹的调理与广泛应用的降低强度调理 (RIC) 白消安方案后的无事件生存期 (EFS) ) 接受异基因造血细胞移植 (HCT)。先前报道的一项包含 476 名患者的随机临床研究的验证性中期分析表明，硫丹在 EFS 方面具有临床意义的改善，具有统计学意义的非劣效性。在这里，呈现了所有 570 名已完成长期随访的随机患者的最终研究结果和预先指定的亚组分析。HCT特异性合并症指数>2或年龄≥50岁的患者被随机分配（1：² IV) 或白消安 (6.4 mg/kg IV) 按疾病风险组、供体类型和参与机构分层后。主要终点是疾病复发、移植失败或任何原因导致的死亡作为事件的 EFS。与 RIC 白消安相比，服用硫丹的患者（中位年龄 60 岁）的 EFS 优于 RIC 白消安：36 个月的 EFS 率为 59.5%（95% CI，52.2-66.1）与 49.7%（95% CI，43.3-55.7），风险比 (HR) 为 0.64 (95% CI, 0.49–0.84), p  = 0.0006。同样，与白消安相比，使用三硫丹的总生存期 (OS) 优于白消安：36 个月的总生存率分别为 66.8% 和 56.3%；HR 0.64 (95% CI, 0.48–0.87), p = 0.0037。事后分析显示，这些差异与确认性中期分析一致，因此硫丹方案似乎特别适合老年 AML 和 MDS 患者。