Azacitidine to treat measurable residual disease in patients with MDS/AML: final long-term results of the RELAZA2 trial

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.

Authors

Institutions

Publication Details

Journal
Blood
Published
2025-12-08
DOI
https://doi.org/10.1182/blood.2025030816
Citations
1
Primary Topic
Acute Myeloid Leukemia Research
Type
article
Field-Weighted Citation Impact
1.77
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Azacitidine to treat measurable residual disease in patients with MDS/AML: final long-term results of the RELAZA2 trial

Rebekka Wehner, Anke Mütherig, Johannes Schetelig, Alwin Krämer et al.
1 citations
Blood
Acute Myeloid Leukemia Research
1.77
article

Azacitidine to treat measurable residual disease in patients with MDS/AML: final long-term results of the RELAZA2 trial

Rebekka Wehner, Anke Mütherig, Johannes Schetelig, Alwin Krämer, Christian Thiede, Matthias Stelljes, Michael Krämer, Tilmann Bochtler, Sebastian Stasik, Uta Oelschlaegel, Christoph Röllig, Martin Bornhäuser, Carsten Müller‐Tidow, Dominik Georg Friedrich Wolf, Claudia Dorothea Baldus, Jan Moritz Middeke, Friedrich Stölzel, Regina Herbst, Mathias Hänel, Eva Eßeling, Katharina S. S. Götze, Lars R. Fransecky, Katja Sockel, Marc Schmitz, Uwe Platzbecker, Richard Noppeney, Ulrich Dührsen, Hubert Serve, Gesine Bug, Malte von Bonin, G. Ehninger, Julia Annabell Georgi, Anna Harig, Anne Sophie Platzbecker
article en
1 citations

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.

BloodVol. 147(10)
Goethe University Frankfurt (DE), Hasso Plattner Institute (DE), Innsbruck Medical University (AT), German Cancer Research Center (DE), Universität Innsbruck (AT), Heidelberg University (DE), University of Münster (DE), University Hospital Heidelberg (DE), TUM Klinikum (DE), Heidelberg University of Education (DE), Krankenhaus der Barmherzigen Brüder Trier (DE), Städtisches Klinikum Dresden (DE), Tyrolean Cancer Research Institute (AT), University Hospital Münster (DE), National Center for Tumor Diseases (DE), University Hospital Schleswig-Holstein (DE), Essen University Hospital (DE), University Hospital Frankfurt (DE), DOCxcellence (Germany) (DE), Medizinische Universität Lausitz - Carl Thiem (DE), University Hospital Carl Gustav Carus (DE), Klinikum Chemnitz (DE), Klinik und Poliklinik für Psychotherapie und Psychosomatik (DE), Clinical Research Center Kiel (DE), Hochschule für Technik und Wirtschaft Dresden – University of Applied Sciences (DE), Technical University of Munich (DE), Technische Universität Dresden (DE), Heidelberg University (US), University of Lübeck (DE)
Openalex Percentile: Top 10%
Acute Myeloid Leukemia Research
1.77
DOISourceOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.