AML-342 A Phase II Study of Azacitidine and Venetoclax as Maintenance Therapy in Patients With Acute Myeloid Leukemia

Context: Patients with acute myeloid leukemia (AML) who achieve remission but do not undergo stem cell transplantation (SCT) experience high relapse rates. Oral azacitidine (CC-486) prolongs relapse-free survival (RFS) and overall survival (OS) in SCT-ineligible patients. The addition of venetoclax may enhance the efficacy of azacitidine within a maintenance regimen. Objective: Establish the efficacy and tolerability of maintenance azacitidine and venetoclax in AML. Design: This is a phase 2, single-center, single-arm study ongoing since 9/2019. The current median follow-up time is 9 months. Patients: AML patients ≥18 years in first remission (CR1) after induction and 1+ consolidation cycles not immediately eligible for SCT were eligible. High- and low-intensity induction regimens were permitted. Patients in CR2 and beyond were eligible if minimal residual disease (MRD)-positive. Interventions: Azacitidine 50 mg/m² IV/SQ x5 days and venetoclax 400 mg x14 days (or 7 days at the discretion of the treating physician in patients at high risk of cytopenias/infections) were administered in 28-day cycles, up to 24 cycles. Main Outcome Measures: RFS (enrollment to death/relapse), OS, and safety/tolerability. Patients who later became eligible for SCT were censored at the time of SCT. Results: Thirty-four patients with a median age of 54 years (19–82) have been enrolled (25 after intensive induction, 9 after low-intensity induction). Thirteen (38%) received 14 days of venetoclax and 21 (62%) received 7 days. The median number of cycles given was 8 (1–24). To date, 9 patients (26%) have relapsed and 6 (18%) have died (all following relapse or SCT). The median RFS was not reached (NR) (1-yr 62.4%) and the median OS was NR (1-yr 84.2%). Eight patients (24%) went off protocol for SCT. Median RFS stratified by ELN 2017 was NR (1-yr 83.1%), NR (1-yr 65.6%), and 4 months in ELN favorable, intermediate, and adverse, respectively. Two of the 7 (29%) MRD(+) patients became MRD(–) on maintenance. The most common grade 3/4 adverse events were infections (26%, including 6% neutropenic fever), thrombocytopenia (21%), and neutropenia (18%). Conclusions: Azacitidine/venetoclax is tolerable and yields encouraging RFS in AML patients not immediately eligible for SCT.