含标准剂量或高剂量柔红霉素的7 + 3方案单诱导或双诱导用于新诊断的急性髓系白血病：白血病研究联盟的随机DaunoDouble试验
Single or Double Induction With 7 + 3 Containing Standard or High-Dose Daunorubicin for Newly Diagnosed AML: The Randomized DaunoDouble Trial by the Study Alliance Leukemia.
作者信息
Röllig Christoph, Steffen Björn, Schliemann Christoph, Mikesch Jan-Henrik, Alakel Nael, Herbst Regina, Hänel Mathias, Noppeney Richard, Hanoun Maher, Kaufmann Martin, Weinbergerova Barbora, Schäfer-Eckart Kerstin, Sauer Tim, Neubauer Andreas, Burchert Andreas, Baldus Claudia D, Mertová Jolana, Jost Edgar, Niemann Dirk, Novák Jan, Krause Stefan W, Scholl Sebastian, Hochhaus Andreas, Held Gerhard, Szotkowski Tomas, Rank Andreas, Schmid Christoph, Fransecky Lars, Kayser Sabine, Schaich Markus, Kramer Michael, Fiebig Frank, Haake Annett, Schetelig Johannes, Middeke Jan Moritz, Stölzel Friedrich, Platzbecker Uwe, Thiede Christian, Müller-Tidow Carsten, Berdel Wolfgang E, Ehninger Gerhard, Mayer Jiri, Serve Hubert, Bornhäuser Martin
机构信息
Department of Internal Medicine I, University Hospital TU Dresden, Dresden, Germany.
Department of Internal Medicine II, University Hospital Frankfurt, Frankfurt, Germany.
出版信息
J Clin Oncol. 2025 Jan;43(1):65-74. doi: 10.1200/JCO.24.00235. Epub 2024 Sep 16.
PURPOSE
To determine the optimal daunorubicin dose and number of 7 + 3 induction cycles in newly diagnosed AML, this randomized controlled trial compared a once daily dose of 60 mg/m with 90 mg/m daunorubicin in the first 7 + 3 induction and one versus two cycles of 7 + 3 induction.
PATIENTS AND METHODS
Patients age 18-65 years with newly diagnosed AML were randomly assigned to 60 versus 90 mg/m daunorubicin once daily plus cytarabine. Patients with marrow blasts below 5% on day 15 after first induction were randomly assigned to receive a second induction cycle or no second induction cycle.
RESULTS
Eight hundred and sixty-four patients with a median age of 52 years were randomly assigned. After a preplanned interim analysis showing no significant difference in response between 60 and 90 mg/m, all consecutive patients received 60 mg/m daunorubicin once daily. The proportion of good early responders was 44% versus 48% ( = .983) with a composite complete remission (CRc) rate of 90% versus 89% after induction ( = .691); the 3-year relapse-free survival (RFS) after 60 versus 90 mg/m once daily was 54% versus 50% ( = .561), and the 3-year overall survival (OS) was 65% versus 58% ( = .242). Among 389 good responders, CRc rates at the end of induction were 87% after single induction and 85% after double induction. The 3-year RFS was 51% versus 60% (hazard ratio [HR], 1.3; = .091), and the 3-year OS was 76% versus 75% after single versus double induction (HR, 1.0; = .937).
CONCLUSION
The use of 90 mg/m daunorubicin once daily in the context of classical 7 + 3 induction does not significantly improve early response and does not lead to higher remission rates or longer survival than 60 mg/m once daily. In patients with a good early response after first induction, a second induction has only a limited impact on RFS and does not result in an OS benefit.
目的
为确定新诊断急性髓系白血病（AML）中柔红霉素的最佳剂量及7 + 3诱导周期数，本随机对照试验比较了在首个7 + 3诱导疗程中，每日一次剂量为60mg/m²与90mg/m²的柔红霉素，以及1个与2个周期的7 + 3诱导疗程。
患者与方法
年龄在18 - 65岁的新诊断AML患者被随机分配接受每日一次剂量为60mg/m²与90mg/m²的柔红霉素加阿糖胞苷治疗。首次诱导后第15天骨髓原始细胞低于5%的患者被随机分配接受第二个诱导周期或不接受第二个诱导周期。
结果
864例中位年龄为52岁的患者被随机分配。在一项预先计划的中期分析显示60mg/m²与90mg/m²之间反应无显著差异后，所有连续入组患者均接受每日一次60mg/m²的柔红霉素治疗。早期良好反应者的比例分别为44%和48%（P = 0.983），诱导后复合完全缓解（CRc）率分别为90%和89%（P = 0.691）；每日一次60mg/m²与90mg/m²治疗后3年无复发生存率（RFS）分别为54%和50%（P = 0.561），3年总生存率（OS）分别为65%和58%（P = 0.242）。在389例良好反应者中，单次诱导后诱导结束时的CRc率为87%，两次诱导后为85%。单次与两次诱导后3年RFS分别为51%和60%（风险比[HR]，1.3；P = 0.091），3年OS分别为76%和75%（HR，1.0；P = 0.937）。
结论
在经典的7 + 3诱导方案中，每日一次使用90mg/m²柔红霉素并不能显著改善早期反应，与每日一次60mg/m²相比，也不会带来更高的缓解率或更长的生存期。在首次诱导后早期反应良好的患者中，第二个诱导周期对RFS的影响有限，且未带来OS获益。
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