Garcia-Manero Guillermo, Podoltsev Nikolai A, Othus Megan, Pagel John M, Radich Jerald P, Fang Min, Rizzieri David A, Marcucci Guido, Strickland Stephen A, Litzow Mark R, Savoie M Lynn, Medeiros Bruno C, Sekeres Mikkael A, Lin Tara L, Uy Geoffrey L, Powell Bayard L, Kolitz Jonathan E, Larson Richard A, Stone Richard M, Claxton David, Essell James, Luger Selina M, Mohan Sanjay R, Moseley Anna, Appelbaum Frederick R, Erba Harry P
Department of Leukemia, MD Anderson Cancer Center, Houston, TX, USA.
Yale School of Medicine, New Haven, CT, USA.
Leukemia. 2024 Jan;38(1):58-66. doi: 10.1038/s41375-023-02073-x. Epub 2023 Nov 7.
Prior experience indicated that use of higher doses of cytarabine during induction for acute myeloid leukemia (AML) with a histone deacetylase inhibitor resulted in high response rates. S1203 was a randomized multicenter trial for previously untreated patients aged 18-60 with AML which compared daunorubicin and cytarabine (DA), idarubicin with higher dose cytarabine (IA) and IA with vorinostat (IA + V). The primary endpoint was event free survival (EFS). 738 patients were randomized: 261 to each DA and IA arms and 216 to the IA + V arm. 96, 456, and 150 patients had favorable-, intermediate-, and unfavorable-risk cytogenetics, respectively. 152 were NPM1 and 158 FLT3 mutated. The overall remission rate was 77.5% including 62.5% CR and 15.0% CRi. No differences in remission, EFS, or overall survival were observed among the 3 arms except for the favorable cytogenetics subset who had improved outcomes with DA and postremission high dose cytarabine. A trend towards increased toxicity was observed with the IA and IA + V arms. The use of higher dose cytarabine during induction therapy in younger patients with AML, with or without vorinostat, does not result in improved outcomes. (Funded by the US National Institutes of Health and others, ClinicalTrials.gov number, NCT01802333.).
既往经验表明，在急性髓系白血病（AML）诱导治疗期间联合使用组蛋白去乙酰化酶抑制剂时，使用更高剂量的阿糖胞苷可带来较高的缓解率。S1203是一项针对18 - 60岁初治AML患者的随机多中心试验，比较了柔红霉素与阿糖胞苷（DA）、伊达比星与高剂量阿糖胞苷（IA）以及IA与伏立诺他（IA + V）。主要终点是无事件生存期（EFS）。738例患者被随机分组：DA组和IA组各261例，IA + V组216例。分别有96例、456例和150例患者具有预后良好、中等和不良风险的细胞遗传学特征。152例患者NPM1突变，158例患者FLT3突变。总缓解率为77.5%，包括62.5%的完全缓解（CR）和15.0%的部分缓解伴血细胞计数未完全恢复（CRi）。除了预后良好的细胞遗传学亚组患者使用DA和缓解后高剂量阿糖胞苷有更好的结局外，三组在缓解率、EFS或总生存期方面未观察到差异。IA组和IA + V组观察到毒性增加的趋势。在年轻AML患者诱导治疗期间使用更高剂量的阿糖胞苷，无论是否联合伏立诺他，均未带来更好的结局。（由美国国立卫生研究院及其他机构资助，ClinicalTrials.gov编号，NCT01802333。）
