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

• MRD-guided azacitidine therapy induces durable long-term responses in patients with MDS and AML

• Over half of initial responders stayed relapse-free for ≥2 years post-treatment and sustained MRD negativity predicts excellent prognosis

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 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 endpoint was the proportion of patients alive and relapse-free six 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 endpoint was met; 60 (63%) patients were relapse-free (95% confidence interval 54-71%, P<0.0001) six months after azacitidine initiation with no new safety signals. Of 60 patients achieving MRD response during the first six cycles of azacitidine, 31 (52%) maintained response without hematological relapse for ≥2 years following azacitidine initiation. The median treatment-free duration following 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 MRDneg, 60-month overall survival and relapse-free survival were 88% and 79%, respectively. Continuously MRDneg patients display a very favorable prognosis. A majority of MRDpos patients can be effectively treated with azacitidine with potential long-term remission even after termination of azacitidine. Clinicaltrials.gov: NCT01462578.