Disease risk but not remission status determines transplant outcomes in AML: long-term outcomes of the ASAP trial
Abstract
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.
Article Details
Authors (36)
Matthias Stelljes
16Department of Medicine A, University Hospital Münster, Münster, Germany
Jan Moritz Middeke
Gesine Bug
13Department of Medicine 2, University Hospital, Goethe University Frankfurt, Frankfurt, Germany
Eva-Maria Wagner-Drouet
4Department of Stem Cell Transplantation, University Hospital Mainz, Mainz, Germany
Lutz P. Müller
4Department of Internal Medicine IV, Hematology and Oncology, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany
Christoph Schmid
Augsburg University Hospital
Stefan W. Krause
7Department of Internal Medicine 5, Universitätsklinikum Erlangen, Erlangen, Germany
Wolfgang Bethge
8Department of Hematology, Oncology, Clinical Immunology, and Rheumatology, University Hospital Tübingen, Tübingen, Germany
Edgar Jost
Uwe Platzbecker
Stefan A. Klein
11Department of Hematology and Oncology, Universitätsmedizin Mannheim, Mannheim, Germany
Judith Niederland
12Klinik für Hämatologie und Zelltherapie, Helios Klinikum Berlin-Buch, Berlin, Germany
Martin Kaufmann
22Department of Hematology, Oncology and Palliative Medicine, Robert Bosch Hospital, Stuttgart, Germany
Kerstin Schäfer-Eckart
25Department of Internal Medicine 5, Oncology, Hematology and Bone Marrow Transplantation, Klinikum Nürnberg Campus Nord, Paracelsus Medical University, Nürnberg, Germany
Henning Baldauf
15Clinical Trials Unit, DKMS Group, Tübingen und Dresden, Germany
Friedrich Stölzel
8Department of Internal Medicine II, Hematology and Oncology, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany
Sarah Trost
15Clinical Trials Unit, DKMS Group, Tübingen und Dresden, Germany
Christoph Röllig
22Department of Internal Medicine I, University Hospital TU Dresden, Dresden, Germany
Malte von Bonin
4Department of Internal Medicine I, University Hospital Dresden, Dresden University of Technology, Dresden, Germany
Katharina Egger-Heidrich
Desiree Kunadt
27Medizinische Klinik und Poliklinik I, University Hospital Carl Gustav Carus Dresden, Technical University of Dresden, Dresden, Germany
Björn Steffen
26Department of Medicine II, Hematology/Oncology, Goethe University Frankfurt, University Hospital, Frankfurt, Germany
Beate Hauptrock
4Department of Stem Cell Transplantation, University Hospital Mainz, Mainz, Germany
Christoph Schliemann
Katja Sockel
4Department of Internal Medicine I, University Hospital Dresden, Dresden University of Technology, Dresden, Germany
Fabian Lang
3Goethe University Frankfurt, University Hospital, Department of Medicine 2, Frankfurt, Germany
Oliver Kriege
4Department of Stem Cell Transplantation, University Hospital Mainz, Mainz, Germany
Judith Schaffrath
4Department of Internal Medicine IV, Hematology and Oncology, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany
Christian Reicherts
1Department of Medicine A, Hematology, Oncology, and Pneumology, University Hospital Münster, Münster, Germany
Wolfgang E. Berdel
Hubert Serve
Gerhard Ehninger
4Department of Internal Medicine I, University Hospital Dresden, Dresden University of Technology, Dresden, Germany
Alexander H. Schmidt
Jan-Henrik Mikesch
1Department of Medicine A, Hematology, Oncology, and Pneumology, University Hospital Münster, Münster, Germany
Martin Bornhäuser
Johannes Schetelig
4Department of Internal Medicine I, University Hospital Dresden, Dresden University of Technology, Dresden, Germany