Disease risk but not remission status determines transplant outcomes in AML: long-term outcomes of the ASAP trial

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Matthias Stelljes - , Universitätsklinikum Münster (Autor:in)
  • Jan Moritz Middeke - , Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus Dresden (Autor:in)
  • Gesine Bug - , Universitätsklinikum Frankfurt (Autor:in)
  • Eva-Maria Wagner-Drouet - , Universitätsmedizin Mainz (Autor:in)
  • Lutz P Müller - , Universitätsklinikum Halle (Autor:in)
  • Christoph Schmid - , Universitätsklinikum Augsburg (Autor:in)
  • Stefan W Krause - , Universitätsklinikum der Friedrich-Alexander-Universität Erlangen-Nürnberg (Autor:in)
  • Wolfgang Bethge - , Universitätsklinikum Tübingen (Autor:in)
  • Edgar Jost - , Universitätsklinikum Aachen (Autor:in)
  • Uwe Platzbecker - , Universitätsklinikum Leipzig (Autor:in)
  • Stefan A Klein - , Universitätsmedizin Mannheim (Autor:in)
  • Judith Niederland - , HELIOS Klinikum Berlin-Buch (Autor:in)
  • Martin Kaufmann - , Robert Bosch Krankenhaus Stuttgart (Autor:in)
  • Kerstin Schäfer-Eckart - , Paracelsus Medizinische Privatuniversität Nürnberg, Klinikum Nürnberg (Autor:in)
  • Henning Baldauf - , DKMS Clinical Trials Unit gGmbH (Autor:in)
  • Friedrich Stölzel - , Universitätsklinikum Schleswig-Holstein Campus Kiel (Autor:in)
  • Sarah Trost - , DKMS Clinical Trials Unit gGmbH (Autor:in)
  • Christoph Röllig - , Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus Dresden (Autor:in)
  • Malte von Bonin - , Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus Dresden (Autor:in)
  • Katharina Egger-Heidrich - , Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus Dresden (Autor:in)
  • Desiree Kunadt - , Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus Dresden (Autor:in)
  • Björn Steffen - , Universitätsklinikum Frankfurt (Autor:in)
  • Beate Hauptrock - , Universitätsmedizin Mainz (Autor:in)
  • Christoph Schliemann - , Universitätsklinikum Münster (Autor:in)
  • Katja Sockel - , Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus Dresden (Autor:in)
  • Fabian Lang - , Universitätsklinikum Frankfurt (Autor:in)
  • Oliver Kriege - , Universitätsmedizin Mainz (Autor:in)
  • Judith Schaffrath - , Universitätsklinikum Halle (Autor:in)
  • Christian Reicherts - , Universitätsklinikum Münster (Autor:in)
  • Wolfgang E Berdel - , Universitätsklinikum Münster (Autor:in)
  • Hubert Serve - , Universitätsklinikum Frankfurt (Autor:in)
  • Gerhard Ehninger - , Cellex GmbH (Autor:in)
  • Alexander H Schmidt - , DKMS Clinical Trials Unit gGmbH (Autor:in)
  • Jan-Henrik Mikesch - , Universitätsklinikum Münster (Autor:in)
  • Martin Bornhäuser - , Medizinische Klinik und Poliklinik I, Universitäts KrebsCentrum Dresden, Universitätsklinikum Carl Gustav Carus Dresden (Autor:in)
  • Johannes Schetelig - , Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus Dresden, DKMS Clinical Trials Unit gGmbH (Autor:in)

Abstract

Attempting to induce a complete remission before allogeneic hematopoietic cell transplant (alloHCT) is current practice in patients with acute myeloid leukemia (AML). However, benefit of remission induction strategy (RIST) before alloHCT has never been proven in a prospective trial. Potent conditioning regimens exist that allow for successful alloHCT in patients with active AML. Therefore, the ASAP trial was conducted to test RIST by salvage chemotherapy before alloHCT against immediate transplant after intensified conditioning. In total, 281 patients with AML with poor response after first induction or untreated first relapse were randomized 1:1 to RIST with high-dose cytarabine plus mitoxantrone vs immediate alloHCT with sequential conditioning after nonintensive disease control (DisC) measures, preferentially watchful waiting only. Overall survival at 5 years from randomization analyzed according to intention-to-treat was 46.1% for DisC vs 47.5% for RIST (P = .82). In multivariable Cox regression analysis, genetic AML risk according to European LeukemiaNet criteria (P < .0001), age (P = .001), and comorbidities (P = .046) predicted survival, but not treatment arm (hazard ratio, 1.08 for DisC vs RIST; P = .67). In conclusion, long-term follow-up of the ASAP trial showed no survival advantage for standard salvage chemotherapy before alloHCT as opposed to immediate alloHCT. The trial results question the general concept of RIST with intensive standard salvage therapy before alloHCT for all patients, because immediate alloHCT may reduce time in hospital and health care expenses. Novel bridging therapies that are well tolerated, and posttransplant maintenance with targeted drugs are urgently warranted, especially for adverse-risk AML, to improve outcomes after alloHCT. This trial was registered at www.ClinicalTrials.gov as #NCT02461537.

Details

OriginalspracheEnglisch
Seiten (von - bis)2293-2305
Seitenumfang13
FachzeitschriftBlood
Jahrgang146
Ausgabenummer19
PublikationsstatusVeröffentlicht - 6 Nov. 2025
Peer-Review-StatusJa

Externe IDs

Scopus 105017672802

Schlagworte

Schlagwörter

  • Humans, Leukemia, Myeloid, Acute/therapy, Female, Male, Middle Aged, Adult, Remission Induction, Hematopoietic Stem Cell Transplantation, Cytarabine/administration & dosage, Aged, Transplantation Conditioning/methods, Young Adult, Treatment Outcome, Adolescent, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Mitoxantrone/administration & dosage, Transplantation, Homologous, Follow-Up Studies, Salvage Therapy, Risk Factors