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458 Remission and Survival after Single Versus Double Induction with 7+3 for Newly Diagnosed Acute Myeloid Leukemia: Results from the Planned Interim Analysis of Randomized Controlled SAL-Daunodouble Trial

Program: Oral and Poster Abstracts
Type: Oral
Session: 613. Acute Myeloid Leukemia: Potpourri of Potential Practice Changing Studies
Hematology Disease Topics & Pathways:
Clinically relevant
Sunday, December 6, 2020: 2:00 PM

Christoph Röllig, MD, MSC1*, Björn Steffen, MD2*, Nael Alakel, MD3*, Regina Herbst, MD4*, Richard Noppeney, MD5*, Maher Hanoun, MD, PhD6*, Zdenek Racil, MD, PhD7*, Kerstin Schäfer-Eckart, MD8*, Alwin Krämer, MD9*, Andreas Neubauer, Professor Dr10, Claudia D Baldus, MD11*, Christoph Schliemann, Prof., MD12*, Martin Kaufmann, MD13, Jolana Mertova14*, Edgar Jost15*, Dirk Niemann, MD16*, Jan Novak17*, Stefan W Krause18*, Sebastian Scholl19,20*, Gerhard Held, Professor Dr21*, Stefani B. Parmentier22, Tomáš Szotkowski, MD, PhD23*, Pavel Zak, MD24*, Andreas Rank, PD Dr25*, Maxi Wass, MD26*, Sebastian Buske27*, Michael Kramer28*, Frank Fiebig29*, Annett Haake29*, Johannes Schetelig, MD, MSc30, Uwe Platzbecker, MD31, Christian Thiede, MD32, Carsten Müller-Tidow, MD33*, Wolfgang E. Berdel, Prof., MD12, Hubert Serve, MD, PhD34, Gerhard Ehninger, MD32, Jiri Mayer35* and Martin Bornhäuser, MD28*

1Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus, Dresden, Germany
2Medizinische Klinik II, Klinikum der J.W. Goethe Universität, Frankfurt am Main, Germany
3University Hospital, Dresden, Germany
4Klinikum Chemnitz, Chemnitz, DEU
5Department of Hematology, University Hospital of Essen, Essen, Germany
6Universitätsklinikum Essen, Essen, DEU
7UHKT, Prague 2, CZE
8Klinik für Innere Medizin V, Klinikum Nürnberg Nord, Nürnberg, Germany
9Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center (DKFZ) and Department of Internal Medicine V, Heidelberg, Germany
10Klinik für Innere Medizin, Schwerpunkt Hämatologie, Onkologie und Immunologie, Philipps University, Marburg, Germany
11Medical Department II, Hematology and Oncology, University Hospital Schleswig-Holstein, Kiel, Germany
12Medizinische Klinik A, Universitätsklinikum Münster, Münster, Germany
13Abteilung für Hämatologie, Onkologie und Palliativmedizin, Robert Bosch Krankenhaus, Stuttgart, Germany
14UHKT, Prague, Czech Republic
15Department of Internal Medicine IV, Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, RWTH Aachen University Hospital, Aachen, Germany
16Department of Internal Medicine, Gemeinschaftsklinikum Mittelrhein, Koblenz, Germany
17University Hospital Kralovske Vinohrady and Third Faculty of Medicine, Charles U, Prague, CZE
18Department of Internal Medicine V, University Hospital Erlangen, Erlangen, Germany
19Department of Hematology and Oncology, Universitätsklinikum Jena, Klinik für Innere Medizin II, Jena, Germany
20University Hospital Jena, Jena, Germany
21Department of Internal Medicine I, Westpfalz-Klinikum, Kaiserslautern, Germany
22Klinik für Hämatologie, Onkologie und Palliativmedizin, Rems-Murr-Klinikum Winnenden, Winnenden, Germany
23Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic
24Charles University and University Hospital Hradec Králové, Hradec Králové, Czech Republic
25Medical Clinic II, University Hospital of Augsburg, Augsburg, Germany
26Hematology and Oncology, University Hospital of Halle (Saale), Halle (Saale), Germany
27Städtisches Krankenhaus Kiel, Kiel, DEU
28Department of Hematology and Oncology, University Hospital Carl Gustav Carus Dresden, Dresden, Germany
29Universitätsklinikum Dresden, Dresden, Germany
30Medizinische Klinik und Poliklinik I, TU Dresden, Dresden, Germany
31Hematology and Cellular Therapy, University Hospital Leipzig, Leipzig, Germany
32Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus der TU Dresden, Dresden, Germany
33Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany
34Medizinische Klinik 2, Hämatologie/Onkologie, Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany
35University Hospital Brno, Czech Republic, Brno, CZE


Double induction using two subsequent 7+3 regimens of cytarabine plus anthracycline is commonly performed in AML patients with an adequate performance status in order to maximize dose intensity upfront. However, for patients with a good early response at day 15 of first induction, there is no prospective randomized evidence on the necessity or value of a second induction cycle.


In order to answer the question if good responders of the first 7+3 induction could be spared a second induction cycle, we set up randomized-controlled SAL DaunoDouble trial. The study prospectively assesses the outcome of patients with a good early response with respect to the number of induction cycles (single versus double). We assumed non-inferiority of single induction in terms of complete remission (CR/CRi) rate, based on a margin of 7.5%. Here, we present the results of the planned interim analysis.


Patients (pts) 18-65 years with newly diagnosed AML, normal cardiac and organ function received a first induction cycle with seven days of cytarabine plus three days of daunorubicin (“7+3”). Response assessment in bone marrow was done on day 15 after the initiation of chemotherapy and confirmed by central review. A blast count <5% was defined as good response. Pts with good response were randomized to receive a second induction cycle (arm D) or no second induction cycle (arm S). Primary endpoint was CR/CRi after completion of induction, secondary endpoints were RFS, and OS.


Between 2014 and 2020, 624 evaluable pts were enrolled and received the first induction cycle with 7+3. A marrow blast clearance below 5% on day 15 was achieved in 298 pts (48%), providing eligibility for randomization. Of these patients, 150 were randomized into arm S and 148 into arm D, respectively. Median age was 52 years, 92% had de novo AML, NPM1 mutation was present in 53%, FLT3-ITD in 25% of pts. Favorable, intermediate and adverse risk (ELN 2017) were present in 56%, 34% and 10% of pts, respectively. CR/CRi rates at the end of induction were 86% after single induction and 85% after double induction. The CR/CRi rates in 224 pre-defined per-protocol pts were 88% versus 91%, resulting in a CR difference of 3% (95%-CI -0.047-0.111; p for non-inferiority test 0.145). After a median follow-up time of 24 months, RFS was slightly but not significantly lower after single induction with a 3-year RFS of 53% versus 64% (HR 1.4, p=0.125), whereas no differences were seen in 3-year OS, with a of rate of 74% versus 75% (HR 1.1, p=0.645) after single versus double induction.


The interim analysis results show that in good responders, the difference between CR rates after single versus double induction was even smaller than the predefined 7.5% margin, suggesting a trend for non-inferiority of single induction, although statistical significance was not reached. The trial continued recruitment. These findings suggest that in good responders, it may be safe to omit a second induction cycle if a second cycle poses a high risk.

Figure. CR + CRi, RFS and OS after randomization to single versus double induction.

Disclosures: Alakel: Pfizer: Consultancy. Jost: Pfizer: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; JAZZ: Other: travel support; Celgene: Other: travel support. Novak: Roche: Consultancy; Janssen: Other: Travel expenses; Takeda: Consultancy; Amgen: Consultancy, Other: Travel expenses; Pfizer: Consultancy; Novartis: Consultancy. Krause: Takeda: Honoraria; Celgene: Other: Travel Support; MSD: Honoraria; Pfizer: Honoraria; Siemens: Research Funding; Gilead: Other: Travel Support. Held: Roche: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding; BMS: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding; MSD: Consultancy; Acrotech: Research Funding; Spectrum: Research Funding; Amgen: Research Funding. Platzbecker: BMS: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Bergenbio: Research Funding; JAZZ: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Janssen: Honoraria, Research Funding. Thiede: AgenDix GmbH: Other: Co-owner and CEO. Müller-Tidow: Daiichi Sankyo: Research Funding; Pfizer: Research Funding, Speakers Bureau; BiolineRx: Research Funding; Janssen-Cilag GmbH: Speakers Bureau.

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