Outpatient Decitabine in Elderly Patients with Acute Myeloid Leukemia (AML).

The treatment of elderly patients with AML remains controversial due to the inferiority of outcomes associated with standard intensive induction regimens. Hypomethylating agents have been shown to improve quality of life and survival in patients with myelodysplastic syndromes and have activity in AML. We report our experience with decitabine in elderly patients with previously untreated or refractory AML.

We conducted a retrospective analysis of 30 patients (11 males and 19 females) with AML who were ineligible for intensive induction chemotherapy and received decitabine (20 mg/m² for 5 days every 28 days). Median age at diagnosis was 67 years (range 40 to 91 years), 28/30 (93.3%) patients were 60 years of age or older. Twelve (40%) patients had cytogenetic abnormalities (7 – unfavorable). ECOG performance status was 0-1 for 26 patients, 2 for 3 patients and 3 for 1 patient. Seven (23.3%) patients had secondary AML and 23 (76.7%) patients had de novo AML, of which 10 demonstrated evidence of multilineage dysplasia on bone marrow biopsy. Eleven (36.7%) patients progressed after prior therapy which included intensive induction therapy in 10 patients (followed by stem cell therapy in 4 patients) and tipifarnib in 1 patient. Nineteen (63.3%) patients received decitabine as first-line therapy. Clearance of blasts from the peripheral blood was monitored and used as an indicator of improved relapse-free survival in AML. Overall survival was defined as the time from the day 1 of decitabine treatment to death.

Patients received a median of 5 cycles of decitabine. Seven patients (23.3%) received ≥10 cycles. All patients received decitabine in the outpatient setting. No hospitalizations were required to administer treatment. Peripheral blood blast clearance was documented in 23 (76.7%) patients including 7 patients who achieved a CR/CRi, and 2 PR. The median time to response was 2 months with median duration of 3 months. Seven patients (23.3%) did not respond to treatment. To date, 19 (63.3%) patients have died after 5-24 months of therapy and 11 (36.7%) remain alive. The median survival was 12 months in all patients (range 4 to 24 months) and 14 months in the 17 patients who received more than 4 cycles of therapy. Overall survival was 82.4% at 6 months and 47.9% at 12 months. Eleven (36.7%) patients survived for >1 year. Seven patients underwent allogeneic stem cell therapy after achieving CR/CRi on decitabine. Three patients received stem cells from siblings or offspring; 3 patients had a matched unrelated donor and 1 patient received umbilical cord stem cells. Three patients are alive after a median follow-up of 12 months. Three patients died of relapsed AML and 1 patient died of infectious complications of transplant.

Decitabine was well tolerated. Ten patients experienced minimal nausea amenable to ondansetron with no documented episodes of vomiting. Seventeen patients developed grade 4 neutropenia and 3 patients grade 4 thrombocytopenia during the course of treatment. Fourteen (46.7%) patients underwent a total of 37 hospitalizations. Common reasons for hospitalizations were: febrile neutropenia (19), pneumonia (6) and thrombocytopenia (3). Sixteen (53.3%) patients never required hospitalization while undergoing treatment. No deaths were attributed to complications related to therapy.

Decitabine administered as an outpatient is an effective treatment option for elderly and high risk patients with AML. It has a favorable chemotherapy-related toxicity profile and is associated with a decreased frequency of hospitalizations. Decitabine may facilitate a subsequent allogeneic transplant in eligible patients and should be considered a treatment option for high risk patients with AML.

Off Label Use: decitabine in AML.