Single or Double Induction With 7 1 3 Containing Standard or High-Dose Daunorubicin for Newly Diagnosed AML: The Randomized DaunoDouble Trial by the Study Alliance Leukemia

Röllig C, Steffen B, Schliemann C, Mikesch JH, Alakel N, Herbst R, Hänel M, Noppeney R, Hanoun M, Kaufmann M, Weinbergerova B, Schäfer-Eckart K, Sauer T, Neubauer A, Burchert A, Baldus CD, Mertová J, Jost E, Niemann D, Novák J, Krause S, Scholl S, Hochhaus A, Held G, Szotkowski T, Rank A, Schmid C, Fransecky L, Kayser S, Schaich M, Kramer M, Fiebig F, Haake A, Schetelig J, Middeke JM, Stölzel F, Platzbecker U, Thiede C, Müller-Tidow C, Berdel WE, Ehninger G, Mayer J, Serve H, Bornhäuser M (2024)

Publication Type: Journal article

Publication year: 2024

Journal

DOI: 10.1200/JCO.24.00235

Abstract

PURPOSE To determine the optimal daunorubicin dose and number of 7 1 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 1 3 induction and one versus two cycles of 7 1 3 induction. PATIENTS AND Patients age 18-65 years with newly diagnosed AML were randomly assigned to METHODS 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 5 .983) with a composite complete remission (CRc) rate of 90% versus 89% after induction (P 5 .691); the 3-year relapse-free survival (RFS) after 60 versus 90 mg/m² once daily was 54% versus 50% (P 5 .561), and the 3-year overall survival (OS) was 65% versus 58% (P 5 .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 5 .091), and the 3-year OS was 76% versus 75% after single versus double induction (HR, 1.0; P 5 .937). CONCLUSION The use of 90 mg/m² daunorubicin once daily in the context of classical 7 1 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.

Authors with CRIS profile

Involved external institutions

Universitätsklinikum Frankfurt am Main (KGU) Germany (DE) Universitätsklinikum Münster Germany (DE) Universitätsklinikum Carl Gustav Carus Dresden Germany (DE) Klinikum Chemnitz Germany (DE) Universitätsklinikum Essen Germany (DE) Robert-Bosch-Krankenhaus Germany (DE) University Hospital Brno Czech Republic (CZ) Paracelsus Medizinische Privatuniversität, Nürnberg Germany (DE) Universitätsklinikum Gießen und Marburg (UKGM) Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) Germany (DE) Fakultní nemocnice Královské Vinohrady Czech Republic (CZ) Universitätsklinikum Jena Germany (DE) Palacky University Olomouc / Univerzita Palackého v Olomouci Czech Republic (CZ) Ruprecht-Karls-Universität Heidelberg Germany (DE) Universitätsklinikum Aachen (UKA) Germany (DE) Gemeinschaftsklinikum Mittelrhein Germany (DE) Westpfalz-Klinikum Germany (DE) Universitätsklinikum Augsburg Germany (DE) Universitätsklinikum Leipzig Germany (DE) Rems-Murr-Kliniken Germany (DE)

How to cite

APA:

Röllig, C., Steffen, B., Schliemann, C., Mikesch, J.H., Alakel, N., Herbst, R.,... Bornhäuser, M. (2024). Single or Double Induction With 7 1 3 Containing Standard or High-Dose Daunorubicin for Newly Diagnosed AML: The Randomized DaunoDouble Trial by the Study Alliance Leukemia. Journal of Clinical Oncology. https://doi.org/10.1200/JCO.24.00235

MLA:

Röllig, Christoph, et al. "Single or Double Induction With 7 1 3 Containing Standard or High-Dose Daunorubicin for Newly Diagnosed AML: The Randomized DaunoDouble Trial by the Study Alliance Leukemia." Journal of Clinical Oncology (2024).

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