A phase 3 trial of azacitidine versus a semi-intensive fludarabine and cytarabine schedule in older patients with untreated acute myeloid leukemia
A phase 3 trial of azacitidine versus a semi-intensive fludarabine and cytarabine schedule in older patients with untreated acute myeloid leukemia
复制标题
DOI：
10.1002/cncr.33403
复制
发表时间：
2021-02-24
期刊：
影响因子：
6.2
通讯作者：
Montesinos, Pau
中科院分区：
文献类型：
--
作者：
Vives, Susana;Martinez-Cuadron, David;Montesinos, Pau
治疗新诊断为急性髓性白血病（AML）的老年患者（>= 65岁）的选择包括强化和减毒化疗、低甲基化药物（含或不含维奈托克）和支持性治疗。该多中心、随机、开放标签、3期临床试验旨在评估氟达拉滨、阿糖胞苷和非格司亭（FLUGA）方案与阿扎胞苷（AZA）方案相比的疗效和安全性。在第1、3、6和9周期后评价缓解。在第9周期后评估可测量残留病（MRD）。当MRD>= 0.01%时，患者继续治疗直至复发或疾病进展。MRD < 0.01%的患者暂停治疗进入随访阶段。结果FLUGA组3个周期后的完全缓解（CR）率明显更好（18% vs 9%; P = 0.04），但9个月时的CR/CR不完全恢复率相似（33% vs 29%; P = 0.41）。在30天或60天的早期死亡率方面，两组之间没有显著差异。FLUGA的血液学毒性更常见，尤其是在诱导期间。AZA组的1年总生存率（OS）和中位OS优于FLUGA组：分别为47%和27%，9.8个月（95%置信区间[CI]，5.6-14个月）和4.1个月（95% CI，2.7-5.5个月; P = 0.005）。AZA组的中位无事件生存期为4.9个月（95%CI，2.8-7个月），FLUGA组为3个月（95%CI，2.5-3.5个月）（P = 0.001）。然而，两组的长期结局均令人失望（3年OS率，10% vs 5%）。本研究支持AZA骨架用于老年AML患者的未来联合治疗。
BACKGROUND Options to treat elderly patients (>= 65 years old) newly diagnosed with acute myeloid leukemia (AML) include intensive and attenuated chemotherapy, hypomethylating agents with or without venetoclax, and supportive care. This multicenter, randomized, open-label, phase 3 trial was designed to assess the efficacy and safety of a fludarabine, cytarabine, and filgrastim (FLUGA) regimen in comparison with azacitidine (AZA).METHODS Patients (n = 283) were randomized 1:1 to FLUGA (n = 141) or AZA (n = 142). Response was evaluated after cycles 1, 3, 6, and 9. Measurable residual disease (MRD) was assessed after cycle 9. When MRD was >= 0.01%, patients continued with the treatment until relapse or progressive disease. Patients with MRD < 0.01% suspended treatment to enter the follow-up phase.RESULTS The complete remission (CR) rate after 3 cycles was significantly better in the FLUGA arm (18% vs 9%; P = .04), but the CR/CR with incomplete recovery rate at 9 months was similar (33% vs 29%; P = .41). There were no significant differences between arms in early mortality at 30 or 60 days. Hematologic toxicities were more frequent with FLUGA, especially during induction. The 1-year overall survival (OS) rate and the median OS were superior with AZA versus FLUGA: 47% versus 27% and 9.8 months (95% confidence interval [CI], 5.6-14 months) versus 4.1 months (95% CI, 2.7-5.5 months; P = .005), respectively. The median event-free survival was 4.9 months (95% CI, 2.8-7 months) with AZA and 3 months (95% CI, 2.5-3.5 months) with FLUGA (P = .001).CONCLUSIONS FLUGA achieved more remissions after 3 cycles, but the 1-year OS rate was superior with AZA. However, long-term outcomes were disappointing in both arms (3-year OS rate, 10% vs 5%). This study supports the use of an AZA backbone for future combinations in elderly patients with AML.