Azacitidine in the Treatment of Elderly Patients with Acute Myelogenous Leukemia

BACKGROUND: Effective treatment of the elderly patient with acute myelogenous leukemia (AML) remains a challenging task. Elderly patients with AML usually respond poorly to standard induction chemotherapy. Response rates in elderly patients are in the range of 30–50% compared to 80–90% in younger patients. Moreover, prolonged hospitalization with treatment related mortality as high as 30% is typical in this older population. In a prior retrospective analysis done at our institution, azacitidine showed an overall response rate of 60% with limited toxicity when administered to patients older than 55 years of age with AML. We present an interim analysis of the first 8 patients enrolled in our prospective, phase II open label study using single agent azacitidine for elderly patients with AML.

METHODS: This is a prospective, phase II open label study using azacitidine in patients ≥ 60 years with AML. Inclusion criteria: Newly diagnosed AML (de novo or secondary, WHO criteria) and ECOG ≤ 2. Promyelocytic (M3) phenotype was excluded. Patients with circulating blast count ≥ 30,000/mcl were treated with hydroxyurea until < 30,000/mcl. Azacitidine was given at a dose of 100 mg/m² subcutaneously for 5 consecutive days every 28 days until disease progression or significant toxicity. G-CSF was given to patients with neutropenia (ANC < 1000/mcl) during all cycles excluding cycle one.

RESULTS: Eight patients have been enrolled to date. The mean age of patients is 74 (range: 64–82 years). The mean baseline ECOG performance score was 1 with a mean during treatment of 1. Mean baseline bone marrow blast count was 53% (range: 21–92%). Overall response rate using the NCI response criteria was 75% (6/8): complete response (CR; n=2; 25%) and partial response (PR; n=4; 50%). The mean number of days on treatment was 117 (range: 4–247 days). The mean number of days hospitalized during therapy was 18 (range: 7–51 days) with the majority of therapy being given in the outpatient setting. The mean overall survival time from diagnosis for all patients was 180 days (range: 23–403). The mean overall survival time for responders was 200 days (range: 36–403). Three patients continue on therapy at 146 (PR), 153 (CR) and 247 (PR) days. Of the other responders, one went on to receive an allogeneic PBSCT, one died at 36 days from complications of a strangulated hernia, and one removed himself from study at 82 days (unconfirmed CR) to receive treatment closer to home. All patients were red blood cell (RBC) transfusion dependent at the start of the therapy. To date, two of the six responders (33%) became independent of RBC transfusion. Four patients were transfusion dependent for platelets at the start of therapy with two being non-responders and two achieving a PR. Non-hematological toxicity was limited to mild injection site skin reaction and fatigue in 63% (5/8) each. No treatment related deaths were observed. The dose and schedule of therapy remained constant in all patients except one who required a 25% dose reduction after cycle 3 due to drug induced marrow suppression.

CONCLUSION: This interim analysis suggests that the administration of subcutaneous azacitidine in an accelerated dosing schedule to elderly patients with acute myelogenous leukemia is a feasible and well-tolerated alternative to standard induction chemotherapy.