> Details

Röllig, Christoph; Steffen, Björn; Alakel, Nael; Herbst, Regina; Noppeney, Richard; Hanoun, Maher; Racil, Zdenek; Schäfer-Eckart, Kerstin; Krämer, Alwin; Neubauer, Andreas; Baldus, Claudia D; Schliemann, Christoph; Kaufmann, Martin; Mertova, Jolana; Jost, Edgar; Niemann, Dirk; Novak, Jan; Krause, Stefan W; Scholl, Sebastian; Held, Gerhard; Parmentier, Stefani B.; Szotkowski, Tomáš; Zak, Pavel; Rank, Andreas; [...]

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

Reference
management

Bookmarks

Remove from
bookmarks

Share this on Whatsapp

Close

Bookmarks



You can manage bookmarks using lists, please log in to your user account for this.
  • Media type: E-Article
  • Title: 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
  • Contributor: Röllig, Christoph; Steffen, Björn; Alakel, Nael; Herbst, Regina; Noppeney, Richard; Hanoun, Maher; Racil, Zdenek; Schäfer-Eckart, Kerstin; Krämer, Alwin; Neubauer, Andreas; Baldus, Claudia D; Schliemann, Christoph; Kaufmann, Martin; Mertova, Jolana; Jost, Edgar; Niemann, Dirk; Novak, Jan; Krause, Stefan W; Scholl, Sebastian; Held, Gerhard; Parmentier, Stefani B.; Szotkowski, Tomáš; Zak, Pavel; Rank, Andreas; [...]
  • imprint: American Society of Hematology, 2020
  • Published in: Blood
  • Language: English
  • DOI: 10.1182/blood-2020-140246
  • ISSN: 0006-4971; 1528-0020
  • Keywords: Cell Biology ; Hematology ; Immunology ; Biochemistry
  • Origination:
  • Footnote:
  • Description: <jats:p>Background</jats:p> <jats:p>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.</jats:p> <jats:p>Aims</jats:p> <jats:p>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.</jats:p> <jats:p>Methods</jats:p> <jats:p>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 &amp;lt;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.</jats:p> <jats:p>Results</jats:p> <jats:p>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.</jats:p> <jats:p>Conclusion</jats:p> <jats:p>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.</jats:p> <jats:p>Figure. CR + CRi, RFS and OS after randomization to single versus double induction.</jats:p> <jats:p /> <jats:sec> <jats:title>Disclosures</jats:title> <jats:p>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:AbbVie: Consultancy, Honoraria; Amgen: Honoraria, Research Funding; Geron: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria. 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.</jats:p> </jats:sec>
  • Access State: Open Access