RELAZA2 final long-term results: MRD-guided preemptive azacitidine in MDS/AML

Final long-term results from the phase II, open-label, multicenter RELAZA2 trial (NCT01462578), evaluating measurable residual disease (MRD)‑guided preemptive azacitidine therapy to prevent relapse in patients with myelodysplastic neoplasms (MDS) or acute myeloid leukemia (AML), were published in Blood by Platzbecker et al. Eligible patients were in complete remission (CR) or CR with incomplete hematologic recovery (CRi) after intensive chemotherapy (IC) or allogeneic hematopoietic stem cell transplantation (allo-HSCT). Of 357 screened patients, 119 became MRD‑positive, of whom 95 were eligible for azacitidine treatment. The primary endpoint was the proportion of patients alive and relapse-free 6 months after azacitidine initiation.

Key data: At 6 months, 63% of eligible patients (n = 60/95) were relapse-free (95% confidence interval [CI], 54–71; p < 0.0001). Among responders (n = 60), 52% remained relapse-free for ≥2 years after initiation, with a median treatment-free interval of 20.8 months after azacitidine discontinuation. At a median follow-up of 6.6 years, 25% of initial responders remained alive and in remission without hematological relapse. In the full cohort, 60-month overall survival (OS) and relapse-free survival (RFS) were 36.5% (95% CI, 27.6–48.1) and 23.5% (95% CI, 16.3–34.0), respectively; responders had improved OS (hazard ratio [HR], 0.586; 95% CI, 0.354–0.968; p = 0.037) and RFS (HR, 0.412; 95% CI, 0.255–0.665; p < 0.0001) vs nonresponders. No new safety signals were reported.

Key learning: MRD-guided azacitidine therapy can effectively prevent or delay relapse in patients with MDS or AML in CR or CRi, with durable long-term remission achievable even after treatment discontinuation.