A Retrospective Study of Decitabine for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia: Lack of Response Observed In a Heavily Pretreated Population

Decitabine is a cytosine analogue approved for use in patients with myelodysplastic syndromes. It is currently under investigation in previously untreated elderly acute myeloid leukemia (AML) patients not considered candidates for intensive chemotherapy. Few published data exist regarding the activity of decitabine in treatment of relapsed or refractory AML patients (RR-AML). We report herein on the efficacy of decitabine in adult patients with RR-AML at our institution.

Patients ≥ 18yo receiving decitabine 20 mg/m² IV daily × 5 days as a single agent for the treatment of RR-AML at Moffitt Cancer Center were included in this retrospective analysis. The WHO definition for AML was used to establish diagnosis at baseline. RR-AML was defined as patients achieving a complete remission (CR) with standard induction chemotherapy who experienced relapse or patients who had received ≥ 2 therapies prior to decitabine initiation without CR. The primary objective was to determine the CR rates, including CR with incomplete count recovery (CRi).Data collected included baseline demographics and disease characteristics such as AML subtype, cytogenetics, number of decitabine cycles administered, bone marrow biopsy results, CR rates, duration of remission, death within first 30 days, reason for decitabine discontinuation, and overall survival (OS). All analyses were conducted using SPSS version 17.0 (SPSS, Inc, Chicago, IL). Descriptive statistics were utilized to estimate CR rates and OS was estimated using the Kaplan-Meier method.

Between May 2006 and December 2009, 19 patients with RR-AML initiated treatment with decitabine. The median age of the study population was 61 yr (range 22–78) and all patients had intermediate or poor risk cytogenetics at time of diagnosis. Patients received a median number of 2 treatment cycles with decitabine. Seventy nine percent received > 3 prior regimens prior to initiation of decitabine. Of these patients, only one had received prior therapy with a hypomethylating agent. No patient achieved CR or CRi. OS was 3.1 months and the mortality at 30 days was 0%. Four patients received decitabine post allogeneic stem cell transplant without response. One patient in the RR-AML group with 10% bone marrow blasts at time of 3^rd relapse has continued decitabine for greater than 2 yrs despite the absence of CR. Decitabine was discontinued in 95% of patients secondary to disease progression or death (n=18/19).

Decitabine has minimal remitting activity in patients with RR-AML indicating that achievement of CR in this setting is an unrealistic goal. Resistance to cytarabine may imply resistance to decitabine given common activation and degradation pathways.

Off Label Use: Decitabine for the treatment of AML. Wetzstein: Eisai: Honoraria, Speakers Bureau. Lancet: Eisai: Consultancy; Celgene: Honoraria.