Measurable residual disease (MRD)-guided azacitidine treatment appears to delay or effectively prevent relapse in patients with myelodyplastic syndromes (MDS) and acute myeloid leukemia (AML), according to results from a phase 2 trial published in The Lancet Oncology.
The relapse prevention with azacitidine (RELAZA2) study (ClinicalTrials.gov Identifier: NCT01462578) was an open label, multicenter, phase 2 trial conducted in Germany. Patients aged 18 years or older who had achieved complete remission of advanced MDS (26 patients) or AML (172 patients) after chemotherapy or allogeneic hematopoietic stem cell transplantation were prospectively screened for MRD for 24 months.
Patients who were confirmed to be in complete remission but were MRD-positive were subcutaneously administered 75 mg/m² azacitidine per day for the first 7 days in a 29-day cycle, for up to 24 cycles. MRD status was retested after 6 cycles. Patients who tested MRD-negative were eased off of the treatment. The primary endpoint was the proportion of patients who were relapse-free 6 months after starting azacitidine therapy.
Of 198 screened patients, 30% (60/198) were MRD-positive, and of those patients, 88% (53/60) were eligible for azacitidine treatment, with an average age of 59 years (range, 52-69; 47% female). The majority of patients (91%, 48/53) had AML. After the first 6 cycles, 58% (31/53) of patients were relapse-free (95% CI: 44%-72%, P <.0001). Of those, 61% (19/31) were MRD-negative and 39% (12/31) were MRD-positive but without relapse.
Infections and gastrointestinal toxicity were common nonhematologic adverse events. Neutropenia was the most common grade 3 or 4 adverse event and was experienced by 85% (45/53) of patients. One patient died from an infection, which may have been due to treatment-related neutropenia. Four patients with no previous history of graft-versus-host disease developed it during the study.
The authors supported “sensible, reliable, and frequent monitoring of MRD as early as possible” and concluded that hypomethylating agents such as azacitidine had the potential to delay or prevent relapse in patients with advanced MDS and AML.
1. Platzbecker U, Middeke JM, Sockel K, et al. Measurable residual disease-guided treatment with azacitidine to prevent haematological relapse in patients with myelodysplastic syndrome and acute myeloid leukaemia (RELAZA2): an open-label, multicentre, phase 2 trial [published online November 12, 2018]. Lancet Oncol. doi: 10.1016/S1470-2045(18)30580-1