在 HLA 单倍体相合造血细胞移植治疗 AML 中，白消安联合氟达拉滨与白消安联合环磷酰胺的比较：一项多中心随机 III 期试验。
Busulfan Plus Fludarabine Compared With Busulfan Plus Cyclophosphamide for AML Undergoing HLA-Haploidentical Hematopoietic Cell Transplantation: A Multicenter Randomized Phase III Trial.
机构信息
Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Clinical Medical Research Center of Hematological Diseases of Guangdong Province, Guangzhou, China.
出版信息
J Clin Oncol. 2023 Oct 10;41(29):4632-4642. doi: 10.1200/JCO.23.00101. Epub 2023 Jun 19.
PURPOSE
The busulfan plus fludarabine (BuFlu) conditioning regimen has lower transplant-related mortality (TRM) than busulfan plus cyclophosphamide (BuCy) in HLA-matched transplantation. We aimed to compare outcomes of the BuFlu regimen with those of the BuCy regimen in HLA-haploidentical hematopoietic cell transplantation (haplo-HCT).
METHODS
We performed an open-label, randomized phase III trial at 12 hospitals in China. Eligible patients with AML (18-65 years) were randomly assigned 1:1 to receive BuFlu (busulfan 0.8 mg/kg four times per day on days -6 to -3; fludarabine 30 mg/m once daily on days -7 to -3) or BuCy (same dose of busulfan; cyclophosphamide 60 mg/kg once daily on days -3 and -2). The primary end point was 1-year TRM in the intention-to-treat population and safety in the per-protocol population. This trial is registered with ClinicalTrials.gov (identifier: NCT02487069) and is complete.
RESULTS
From November 20, 2015, to September 30, 2019, 386 patients were randomly assigned to receive the BuFlu (n = 194) or BuCy (n = 192) regimen. The median follow-up was 55.0 (IQR, 46.5-69.0) months after random assignment. The 1-year TRM was 7.2% (95% CI, 4.1 to 11.4) and 14.1% (95% CI, 9.6 to 19.4; hazard ratio [HR], 0.51; 95% CI, 0.27 to 0.97; = .041), the 5-year relapse was 17.9% (95% CI, 9.6 to 28.3) and 14.2% (95% CI, 9.1 to 20.5; HR, 1.12; 95% CI, 0.65 to 1.95; = .670), and the 5-year overall survival was 72.5% (95% CI, 62.2 to 80.4) and 68.2% (95% CI, 58.9 to 75.9; HR, 0.84; 95% CI, 0.56 to 1.26; = .465) in two groups, respectively. Grade 3 regimen-related toxicity (RRT) was reported for 0 of 191 patients following the BuFlu regimen and 9 (4.7%) of 190 patients following the BuCy regimen ( = .002). At least one type of grade 3-5 adverse event was reported for 130 (68.1%) of the 191 patients and 147 (77.4%) of the 190 patients in two groups, respectively ( = .041).
CONCLUSION
The BuFlu regimen has a lower TRM and RRT and similar relapse for patients with AML undergoing haplo-HCT compared with the BuCy regimen.
目的
在 HLA 匹配移植中，与白消安加环磷酰胺（BuCy）方案相比，白消安加氟达拉滨（BuFlu）方案具有较低的移植相关死亡率（TRM）。我们旨在比较 BuFlu 方案与 BuCy 方案在 HLA 单倍体造血细胞移植（haplo-HCT）中的结果。
方法
我们在中国 12 家医院进行了一项开放性、随机、III 期临床试验。符合条件的 AML 患者（18-65 岁）被随机分配 1:1 接受 BuFlu（白消安 0.8mg/kg，每日 4 次，于-6 至-3 天；氟达拉滨 30mg/m2，每日 1 次，于-7 至-3 天）或 BuCy（相同剂量的白消安；环磷酰胺 60mg/kg，每日 1 次，于-3 和-2 天）。主要终点为意向治疗人群中的 1 年 TRM 和方案人群中的安全性。这项试验在 ClinicalTrials.gov （标识符：NCT02487069）注册，现已完成。
结果
自 2015 年 11 月 20 日至 2019 年 9 月 30 日，386 名患者被随机分配接受 BuFlu（n=194）或 BuCy（n=192）方案治疗。随机分组后中位随访时间为 55.0（IQR，46.5-69.0）个月。1 年 TRM 为 7.2%（95%CI，4.1 至 11.4）和 14.1%（95%CI，9.6 至 19.4；风险比[HR]，0.51；95%CI，0.27 至 0.97； =.041），5 年复发率为 17.9%（95%CI，9.6 至 28.3）和 14.2%（95%CI，9.1 至 20.5；HR，1.12；95%CI，0.65 至 1.95； =.670），5 年总生存率为 72.5%（95%CI，62.2 至 80.4）和 68.2%（95%CI，58.9 至 75.9；HR，0.84；95%CI，0.56 至 1.26； =.465）。两组分别有 0 名（0%）和 9 名（4.7%）患者在 BuFlu 方案后出现 3 级方案相关毒性（RRT）（ =.002）。两组分别有 130 名（68.1%）和 147 名（77.4%）患者报告至少有 1 种 3-5 级不良事件（ =.041）。
结论
与 BuCy 方案相比，AML 患者接受单倍体造血细胞移植时，BuFlu 方案的 TRM 和 RRT 较低，复发率相似。
Zotero 插件