Reduced-Dose Azacitidine Plus Venetoclax as Maintenance Therapy for Patients With AML Following Intensive or Low-Intensity Induction

Results from a single-center, phase 2 trial

According to a single-center phase 2 trial, low-dose azacitidine plus venetoclax was found to be a feasible maintenance strategy for patients with acute myeloid leukemia following intensive and low-intensity induction.

“Patients with acute myeloid leukaemia have high rates of relapse, especially if they are unable to complete standard consolidation strategies or allogeneic hematopoietic stem-cell transplantation (HSCT),” explained Alexandre Bazinet, MD, The University of Texas MD Anderson Cancer Center, Houston, Texas, and colleagues. “We aimed to evaluate the efficacy and safety of low dose azacitidine plus venetoclax as maintenance therapy in acute myeloid [leukemia].”

Researchers enacted this single-arm study with eligible patients 18 years of age or older who had a World Health Organization (WHO) 2016 diagnosis of acute myeloid leukemia in complete remission or complete remission with incomplete blood count recovery following intensive or low-intensity induction, and not immediately eligible for HSCT. For participants, their Eastern Cooperative Oncology Group (ECOG) performance status had to be 3 or less. Patients were assigned to maintenance therapy with azacitidine 50 mg/m² intravenously or subcutaneously for 5 days and venetoclax 400 mg orally for 7 days or 14 days. Relapse-free survival was the primary outcome measured.

During the study period between September 2019, and October 2022, 35 patients were enrolled, of whom 25 (71%) were assigned to cohort 1 following intensive induction and 10 (29%) to cohort 2 following low-intensity induction. The median number of cycles distributed to patients was 9 (interquartile range [IQR] 2 to 22) and the median follow-up time was 23.3 months (IQR 9.0 to 30.0). The median relapse-free survival was not reached (95% confidence interval [CI], 20.2 to not calculable) in the full cohort, not reached (29.1 to not calculable) in cohort 1, and 30.3 months (16.5 to not calculable) in cohort 2. The 2-year relapse-free survival was found to be 65% (95% CI, 50 to 85) in the full cohort, 71% (53 to 94) in cohort 1, and 52% (27 to 100) in cohort 2.

As far as safety, the most common grade 3 to 4 treatment-emergent adverse events were noted to be thrombocytopenia (n=6), lung infection (n=4), leukopenia (n=4), and neutropenia (n=3). No deaths occurred during maintenance therapy. Researchers ended the study early due to slow accrual, and all patients who participated were included in these efficacy and safety analyses. 

“Low dose azacitidine plus venetoclax is a feasible maintenance strategy in acute myeloid [leukemia] following intensive and low-intensity induction,” Bazinet and coauthors concluded.

Source:

Bazinet A, Kantarjian H, Bataller A, et al. Reduced dose azacitidine plus venetoclax as maintenance therapy in acute myeloid leukaemia following intensive or low-intensity induction: a single-centre, single-arm, phase 2 trial. Lancet Haematol. Published online April 2024. doi:10.1016/S2352-3026(24)00034-6