Maintenance therapy with azacitidine (Onureg) tablets improved overall survival (OS) in patients with acute myeloid leukemia (AML) who were in remission after intensive chemotherapy in the phase 3 QUAZAR AML-001 study. Survival was extended regardless of the patients’ measurable residual disease (MRD) status at study entry, reported Gail J. Roboz, MD, Director, Clinical and Translational Leukemia Program, Weill Medical College of Cornell University, New York, NY, at ASH 2020.
“MRD is extremely important in AML, and it’s clear that the presence of MRD in the bone marrow of patients with AML in remission after intensive chemotherapy is predictive of early relapse,” Dr Roboz emphasized. Remission rates are high in patients with AML who receive intensive chemotherapy, but the response to treatment is often temporary.
“Maintenance therapy with oral azacitidine improves overall survival and relapse-free survival, independent of MRD status, and can induce MRD negativity in MRD-positive patients after intensive chemotherapy,” said Dr Roboz.
In the QUAZAR AML-001 maintenance study, the median OS was prolonged with oral azacitidine compared with placebo in patients with MRD-positive or MRD-negative status. The median OS was 14.6 months versus 10.4 months, respectively, hazard ratio (HR), 0.69 (95% confidence interval [CI], 0.51-0.93) or 30.1 months versus 24.3 months, HR, 0.81 (95% CI, 0.59-1.12).
QUAZAR AML-001 was an international, double-blind phase 3 study that enrolled 472 patients with AML and intermediate or poor cytogenetics who had achieved a first complete response or complete response with incomplete count recovery after intensive induction chemotherapy (with or without consolidation treatment). Patients who were candidates for hematopoietic stem-cell transplant at the time of screening were excluded. The patients were randomized in a 1:1 ratio to oral azacitidine or to placebo.
MRD status was determined in 463 of the 472 patients. At baseline, 44% of the patients in the oral azacitidine arm and 51% in the placebo arm had MRD-positive disease. The baseline characteristics were similar between the 2 treatment arms and between the subgroups of patients who had MRD-positive or MRD-negative disease at study entry.
The median duration of MRD negativity was 11 months with oral azacitidine versus 5 months with placebo (HR, 0.62; 95% CI, 0.48-0.78). Patients in the azacitidine cohort also had a higher rate of MRD conversion (37%) from positive to negative versus placebo (19%).
In the oral azacitidine arm, the median relapse-free survival was 7.1 months in patients with MRD-positive AML compared with 2.7 months in patients receiving placebo (HR, 0.58; 95% CI, 0.43-0.78). The rate was similar among the MRD-negative patients: 13.4 months versus 7.8 months, respectively (HR, 0.71; 95% CI, 0.52-0.98).
In multivariate analysis, oral azacitidine showed a significant benefit in OS versus placebo (P = .0067) and in relapse-free survival (P <.0001), independent of baseline MRD status.
Among responders with MRD status at baseline, 9 of 38 (24%) patients randomized to oral azacitidine achieved MRD negativity more than 6 months after randomization compared with only 1 of 22 (5%) patients in the placebo arm.
The results of a second study based on a post-hoc analysis of data from QUAZAR AML-001 were presented at ASH 2020 by Esther Natalie Oliva, MD, Division of Hematology, Azienda Ospedaliena (B-M-M), Bologna, Italy.
The results showed that treatment with azacitidine tablets was associated with a reduced risk for hospitalization events and number of days in the hospital, as well as estimated costs associated with hospitalizations, compared with placebo, Dr Oliva said. Hospitalization days and events in the overall QUAZAR AML-001 cohort were adjusted for the duration of exposure to oral azacitidine and to placebo, she said.
In all, 108 (45.8%) patients in the oral azacitidine arm and 118 (50.6%) in the placebo arm were hospitalized during the study. The exposure-adjusted rate of hospitalization was significantly lower in the oral azacitidine arm versus the placebo arm: 0.48 per patient-year versus 0.64 per patient-year, respectively (relative risk [RR], 0.740; P = .0068).
A total of 2872 hospitalization days occurred in the oral azacitidine arm versus 3139 hospitalization days in the placebo arm. Most hospitalizations were related to adverse events.
The exposure-adjusted days-in-hospital rate was significantly lower among patients assigned to oral azacitidine compared with placebo: 7.89 per patient-year versus 13.36 per patient-year, respectively (RR, 0.591; P <.0001).
Based on exposure-adjusted days in hospital in the 2 arms, the estimated mean costs of hospitalization in the QUAZAR AML-001 study were $56,224 annually in the oral azacitidine arm versus $95,201 annually in the placebo arm.
“Cumulative cost-savings with oral azacitidine compared with placebo ranged from $2837 in month 2 to $40,909 by month 24,” said Dr Oliva. “The significant improvement in relapse-free survival with oral azacitidine may translate into substantial economic benefits associated with reduced rates of hospitalization and fewer days in hospital, and potentially, lower costs related to administration of salvage chemotherapy.”
