MRD-Guided Azacitidine Treatment in Myelodysplastic Syndrome and Acute Myeloid Leukemia


Key Points

  • 58% of MRD-positive patients receiving azacitidine were relapse-free at 6 months.
  • Relapse-free survival was 46% at 1 year.

In a German phase II trial (RELAZA2) reported in The Lancet Oncology, Platzbecker et al found that minimal residual disease (MRD)–guided treatment with azacitidine was successful in preventing hematologic relapse in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).

Study Details

In the multicenter study, with enrollment between October 2011 and August 2015, 198 adult patients with advanced MDS (n = 26) or AML (n = 172) who had achieved complete remission with conventional chemotherapy or allogeneic hematopoietic stem cell transplantation underwent 24 months of screening for MRD. Patients who developed detectable MRD were given subcutaneous azacitidine 75 mg/m2 per day on days 1 to 7 of 29-day cycles for 24 cycles.

The primary endpoint was the proportion of patients who were relapse-free and alive at 6 months after the start of azacitidine treatment.

Development of MRD and Relapse-Free Survival

Among the 198 patients, 60 (30%) developed detectable MRD during the 24-month screening period, with 53 (88%) being eligible to start azacitidine treatment. At 6 months after the start of azacitidine, 31 (58%) of the 53 patients were relapse-free and alive (a rate greater than the null hypothesis rate of 30% in MRD-positive patients based on prior studies). Of responders, 19 (61%) had a major response (MRD-negative). At median follow-up of 13 months, 12-month relapse-free survival in patients receiving azacitidine was 46%. Among the 138 patients not developing detectable MRD during screening, 12-month relapse-free survival was 88% (hazard ratio = 6.6, P < .0001, for 60 MRD-positive patients vs MRD-negative patients).


The most common grade 3 or 4 adverse events in patients receiving azacitidine were neutropenia (85%), leukopenia (32%), and infection (8%). One patient with neutropenia died due to infection considered possibly related to study treatment.

The investigators concluded, “Preemptive therapy with azacitidine can prevent or substantially delay hematological relapse in MRD-positive patients with MDS or AML who are at high risk of relapse. Our study also suggests that continuous MRD negativity during regular MRD monitoring might be prognostic for patient outcomes.”

The study was funded by Celgene Pharma, Jose Carreras Leukaemia Foundation, National Center for Tumor Diseases (NCT), and German Cancer Consortium (DKTK) Foundation.

Uwe Platzbecker, MD, of Medical Clinic and Policinic 1, Hematology and Cellular Therapy, University Hospital Leipzig, is the corresponding author for The Lancet Oncology article.

Disclosure: See study authors’ full disclosures at

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