Azacitidine to treat measurable residual disease in patients with MDS/AML: final long-term results of the RELAZA2 trial
Abstract
Abstract Measurable residual disease (MRD) can predict relapse in patients with advanced myelodysplastic neoplasms (MDS) or acute myeloid leukemia (AML). We report the long-term efficacy and safety of MRD-guided preemptive azacitidine treatment to prevent relapse in the phase 2 Relapse Prevention With Azacitidine (RELAZA2) trial. Patients with MDS or AML after either intensive chemotherapy only or consecutive allogeneic stem cell transplantation were prospectively screened for imminent relapse by molecular MRD assessment. Patients who became MRD positive (MRDpos) during screening received azacitidine for up to 2 years to prevent relapse. The primary end point was the proportion of patients alive and relapse-free 6 months after azacitidine start. Of 357 patients screened, 119 (33.3%) became MRDpos, of whom 95 (79.8%) were eligible for azacitidine treatment. The primary end point was met; 60 (63%) patients were relapse free (95% confidence interval, 54-71; P< .0001) 6 months after azacitidine initiation with no new safety signals. Of 60 patients achieving MRD response during the first 6 cycles of azacitidine, 31 (52%) maintained response without hematological relapse for ≥2 years after azacitidine initiation. The median treatment-free duration after azacitidine discontinuation was 20.8 months; the longest ongoing response was 104 months. After a median follow-up of 6.6 years, 15 initial responders (25%) remained alive and in remission. Among screened patients who remained continuously MRD negative, 60-month overall survival and relapse-free survival were 88% and 79%, respectively. Patients with continuously negative MRD display a very favorable prognosis. Most patients with MRD positivity can be effectively treated with azacitidine with potential long-term remission even after termination of azacitidine. This trial was registered at www.clinicaltrials.gov as #NCT01462578.
Article Details
Authors (34)
Anne Sophie Platzbecker
1Else Kroener Fresenius Center for Digital Health, Faculty of Medicine and University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany
Julia-Annabell Georgi
4Department of Internal Medicine I, University Hospital Dresden, Dresden University of Technology, Dresden, Germany
Jan Moritz Middeke
Katja Sockel
4Department of Internal Medicine I, University Hospital Dresden, Dresden University of Technology, Dresden, Germany
Rebekka Wehner
Regina Herbst
7Department III of Internal Medicine, Klinikum Chemnitz, Chemnitz, Germany
Dominik Wolf
Claudia D. Baldus
Uta Oelschlägel
4Department of Internal Medicine I, University Hospital Dresden, Dresden University of Technology, Dresden, Germany
Anke Mütherig
4Department of Internal Medicine I, University Hospital Dresden, Dresden University of Technology, Dresden, Germany
Lars Fransecky
14Department of Internal Medicine II, University Hospital Schleswig Holstein, Campus Kiel, Kiel, Germany
Richard Noppeney
11Division of Hematology/Oncology, Medizinische Klinik I, Krankenhaus der Barmherzigen Brüder, Trier, Germany
Gesine Bug
13Department of Medicine 2, University Hospital, Goethe University Frankfurt, Frankfurt, Germany
Katharina S. Götze
Alwin Krämer
Tilmann Bochtler
Matthias Stelljes
16Department of Medicine A, University Hospital Münster, Münster, Germany
Eva Eßeling
19Department of Medicine A, Hematology, Oncology, and Respiratory Medicine, University Hospital Münster, Münster, Germany
Friedrich Stölzel
8Department of Internal Medicine II, Hematology and Oncology, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany
Malte von Bonin
4Department of Internal Medicine I, University Hospital Dresden, Dresden University of Technology, Dresden, Germany
Hubert Serve
Mathias Hänel
7Department III of Internal Medicine, Klinikum Chemnitz, Chemnitz, Germany
Ulrich Dührsen
Anna Harig
4Department of Internal Medicine I, University Hospital Dresden, Dresden University of Technology, Dresden, Germany
Carsten Müller-Tidow
Johannes Schetelig
4Department of Internal Medicine I, University Hospital Dresden, Dresden University of Technology, Dresden, Germany
Sebastian Stasik
4Department of Internal Medicine I, University Hospital Dresden, Dresden University of Technology, Dresden, Germany
Christoph Röllig
22Department of Internal Medicine I, University Hospital TU Dresden, Dresden, Germany
Gerhard Ehninger
4Department of Internal Medicine I, University Hospital Dresden, Dresden University of Technology, Dresden, Germany
Michael Krämer
Marc Schmitz
Martin Bornhäuser
Uwe Platzbecker
Christian Thiede
7University Hospital, Dresden University of Technology, Dresden, Germany