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.

IF 42.1 1区医学 Q1 ONCOLOGY Journal of Clinical Oncology Pub Date : 2025-01-01 Epub Date: 2024-09-16 DOI:10.1200/JCO.24.00235

Christoph Röllig, Björn Steffen, Christoph Schliemann, Jan-Henrik Mikesch, Nael Alakel, Regina Herbst, Mathias Hänel, Richard Noppeney, Maher Hanoun, Martin Kaufmann, Barbora Weinbergerova, Kerstin Schäfer-Eckart, Tim Sauer, Andreas Neubauer, Andreas Burchert, Claudia D Baldus, Jolana Mertová, Edgar Jost, Dirk Niemann, Jan Novák, Stefan W Krause, Sebastian Scholl, Andreas Hochhaus, Gerhard Held, Tomas Szotkowski, Andreas Rank, Christoph Schmid, Lars Fransecky, Sabine Kayser, Markus Schaich, Michael Kramer, Frank Fiebig, Annett Haake, Johannes Schetelig, Jan Moritz Middeke, Friedrich Stölzel, Uwe Platzbecker, Christian Thiede, Carsten Müller-Tidow, Wolfgang E Berdel, Gerhard Ehninger, Jiri Mayer, Hubert Serve, Martin Bornhäuser

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Abstract

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/m² with 90 mg/m² 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/m² 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/m², all consecutive patients received 60 mg/m² daunorubicin once daily. The proportion of good early responders was 44% versus 48% (P = .983) with a composite complete remission (CRc) rate of 90% versus 89% after induction (P = .691); the 3-year relapse-free survival (RFS) after 60 versus 90 mg/m² once daily was 54% versus 50% (P = .561), and the 3-year overall survival (OS) was 65% versus 58% (P = .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; P = .091), and the 3-year OS was 76% versus 75% after single versus double induction (HR, 1.0; P = .937).

Conclusion: The use of 90 mg/m² 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/m² 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.

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对新诊断的急性髓细胞白血病采用含标准剂量或高剂量多柔比星的 7+3 单药或双药诱导：白血病研究联盟的随机 DaunoDouble 试验。

目的：为了确定新诊断的急性髓细胞性白血病患者的最佳多柔比星剂量和7 + 3诱导周期数，本随机对照试验比较了首次7 + 3诱导中每日一次60 mg/m2与90 mg/m2多柔比星的剂量，以及7 + 3诱导一个周期与两个周期：年龄在18-65岁之间的新诊断急性髓细胞白血病患者被随机分配到60 mg/m2与90 mg/m2每日一次的达乌鲁比星和阿糖胞苷治疗方案中。首次诱导后第15天骨髓细胞数低于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：随机分配了 864 名患者，中位年龄为 52 岁。预先计划的中期分析表明，60 毫克/平方米和 90 毫克/平方米之间的反应无显著差异，随后所有患者均接受了 60 毫克/平方米、每天一次的多诺比星治疗。早期良好反应者的比例为44%对48%（P = .983），诱导后的综合完全缓解（CRc）率为90%对89%（P = .691）；60毫克/平方米和90毫克/平方米每日一次治疗后的3年无复发生存率（RFS）为54%对50%（P = .561），3年总生存率（OS）为65%对58%（P = .242）。在389名良好反应者中，单诱导后诱导结束时的CRc率为87%，双诱导后为85%。3年RFS为51%对60%（危险比[HR]，1.3；P = .091），3年OS为76%对75%（HR，1.0；P = .937）：结论：在经典的 7+3 诱导治疗中，每日一次使用 90 毫克/平方米的多诺比星并不能显著改善早期反应，与每日一次使用 60 毫克/平方米的多诺比星相比，也不能带来更高的缓解率或更长的生存期。对于第一次诱导后早期反应良好的患者，第二次诱导对RFS的影响有限，也不会带来OS方面的益处。

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来源期刊

Journal of Clinical Oncology 医学-肿瘤学

CiteScore

41.20

自引率

2.20%

发文量

8215

审稿时长

2 months

期刊介绍： The Journal of Clinical Oncology serves its readers as the single most credible, authoritative resource for disseminating significant clinical oncology research. In print and in electronic format, JCO strives to publish the highest quality articles dedicated to clinical research. Original Reports remain the focus of JCO, but this scientific communication is enhanced by appropriately selected Editorials, Commentaries, Reviews, and other work that relate to the care of patients with cancer.