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

Author(s): Christoph Röllig, MD, MSc¹; Björn Steffen, MD²; Christoph Schliemann, MD³; Jan-Henrik Mikesch, MD³; Nael Alakel, MD¹; Regina Herbst, MD⁴; Mathias Hänel, MD⁴; Richard Noppeney, MD⁵; Maher Hanoun, MD⁵; Martin Kaufmann, MD⁶; Barbora Weinbergerova, MD⁷; Kerstin Schäfer-Eckart, MD⁸; Tim Sauer, MD⁹; Andreas Neubauer, MD¹⁰; Andreas Burchert, MD¹⁰; Claudia D. Baldus, MD¹¹; Jolana Mertová, MD¹²; Edgar Jost, MD¹³; Dirk Niemann, MD¹⁴; Jan Novák, MD¹⁵; Stefan W. Krause, MD¹⁶; Sebastian Scholl, MD¹⁷; Andreas Hochhaus, MD¹⁷; Gerhard Held, MD¹⁸; Tomas Szotkowski, MD¹⁹; Andreas Rank, MD²⁰; Christoph Schmid, MD²⁰; Lars Fransecky, MD¹¹; Sabine Kayser, MD²¹; Markus Schaich, MD²²; Michael Kramer, MSc¹; Frank Fiebig, MSc¹; Annett Haake, BSN¹; Johannes Schetelig, MD¹; Jan Moritz Middeke, MD¹; Friedrich Stölzel, MD¹¹; Uwe Platzbecker, MD²¹; Christian Thiede, MD^1,23; Carsten Müller-Tidow, MD⁹; Wolfgang E. Berdel, MD³; Gerhard Ehninger, MD¹; Jiri Mayer, MD⁷; Hubert Serve, MD²; Martin Bornhäuser, MD¹

Source: https://doi.org/10.1200/JCO.24.00235

Dr. Anjan Patel's Thoughts

This study compared double induction vs. standard induction and a reduced dose of daunorubicin 90mg/m2 vs. 60mg/m2. The reduced dose was just as efficacious and double inductions do not seem to be beneficial. Probably less is more in this setting and once you get the CR, one can move forward with consolidation and start planning for transplant.

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.

Author Affiliations

¹Department of Internal Medicine I, University Hospital TU Dresden, Dresden, Germany; ²Department of Internal Medicine II, University Hospital Frankfurt, Frankfurt, Germany; ³Department of Medicine A, University Hospital Münster, Münster, Germany; ⁴Department of Internal Medicine III, Chemnitz Hospital, Chemnitz, Germany; ⁵Department of Hematology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany; ⁶Department of Hematology, Robert-Bosch-Krankenhaus, Stuttgart, Germany; ⁷Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic; ⁸Department of Internal Medicine V, Nuremberg Hospital North, Paracelsus Medical University, Nuremberg, Germany; ⁹Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany; ¹⁰Department of Internal Medicine, Hematology, Oncology and Immunology, University Hospital Marburg, Marburg, Germany; ¹¹Department of Hematology and Oncology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany; ¹²Institute of Hematology and Blood Transfusion, Prague, Czech Republic; ¹³Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, University Hospital Aachen & CIO ABCD Aachen, RWTH Aachen, Aachen, Germany; ¹⁴Department of Hematology, Oncology and Palliative Care, Gemeinschaftsklinikum Mittelrhein, Koblenz, Germany; ¹⁵Department of Haematology, 3rd Faculty of Medicine, Charles University and University Hospital Kralovske Vinohrady, Hràdec Kralovè, Czech Republic; ¹⁶Department of Internal Medicine V, Universitätsklinikum Erlangen, Erlangen, Germany; ¹⁷Klinik für Innere Medizin, Universitätsklinikum Jena, Jena, Germany; ¹⁸Klinik für Innere Medizin 1, Westpfalzklinikum, Kaiserslautern, Germany; ¹⁹Department of Hemato-Oncology, Palacký University, Olomouc, Czech Republic; ²⁰II. Medizinische Klinik, Universitätsklinikum Augsburg, Augsburg, Germany; ²¹Department of Internal Medicine I, Hematology and Cellular Therapy, University Hospital Leipzig, Leipzig, Germany; ²²Department of Hematology, Oncology and Palliative Care, Rems-Murr-Kliniken, Winnenden, Germany; ²³Agendix GmbH, Dresden, Germany;

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