Treatment options for older patients with acute myeloid leukemia (AML) and for relapsed/refractory patients of any age with AML are limited, and outcomes are generally poor. These patients are often ineligible for intensive anti-leukemic therapy or clinical trial participation due to poor performance status and/or inadequate organ function. Among untreated patients over age 60 years with a good performance status, 40–50% can achieve a complete response, but cure rates are < 10% and median overall survival is under 1 year [1
]. For older patients with adverse prognostic features, such as poor performance status, unfavorable cytogenetics or an antecedent hematologic disorder, expected rates of complete response (CR) are < 20%, early mortality can be as high as 50% and 1-year survival is < 10% [3
]. For patients whose first CR is < 1 year, the probability of obtaining a second CR is 10–20% [5
] Furthermore, even for younger patients able to undergo intensive chemotherapy salvage, the overall survival is < 40% at 2 years [6
Decitabine (5-aza-2'-deoxycytidine; Dacogen) was approved by the United States Food and Drug Administration for the treatment of myelodysplastic syndrome (MDS) on the basis of its ability to improve hematologic and quality of life parameters. It is generally well tolerated, with a favorable extramedullary toxicity profile and infrequent treatment-related mortality. Decitabine is activated intracellularly by deoxycytidine kinase and other nucleotide kinases to the active metabolite 5-aza-2'-deoxycytidine-triphosphate (5-aza-2'-dCTP), which can be incorporated into DNA during the S-phase of the cell cycle. Decitabine is believed to exert its antineoplastic effects by inhibition of DNA methyltransferases, causing DNA hypomethylation and activation of genes involved in differentiation and apoptosis. Although early studies established the safety and efficacy of decitabine at doses up to 3000 mg/m2, more recent work has focused on lower total doses (100–200 mg/m2) sufficient to induce DNA hypomethylation and myeloid differentiation.
Decitabine demonstrated single-agent efficacy in a phase II multicenter study of older patients with AML, with a CR rate of 25%, 30-day mortality of 7%, median overall survival 7.7 months and little extramedullary toxicity when administered using a schedule of 20 mg/m2
over 1 h daily for 5 days [7
]. Patients received a median of three cycles of treatment, with a range of 1–25 cycles. Decitabine administered in the same dose and schedule was shown to have a modest survival benefit over low-dose cytarabine and supportive care (7.7 months decitabine vs. 5.0 months, hazard ratio [HR] = 0.82, p
= 0.037) in a randomized trial of 485 newly diagnosed older patients with AML [8
Blum et al
. treated 53 newly diagnosed patients with AML (median 74 years, range 60–85) with decitabine 20 mg/m2
daily for 10 days every 4 weeks, with 47% CR after a median of 3 cycles [9
]. Induction mortality was 2% within 30 days and 15% within 8 weeks, mostly due to disease progression. Median overall and disease-free survivals were 55 and 46 weeks, respectively. Unlike with low-dose cytarabine, patients with unfavorable features, including complex cytogenetic abnormalities and baseline hyperleukocytosis, achieved a CR.
The objective of this study was to review the treatment outcomes of newly diagnosed older patients with AML and patients with relapsed AML aged ≥ 18 years treated with decitabine at Weill Cornell Medical Center/The New York Presbyterian Hospital. Many were ineligible for standard chemotherapy or investigational trials due to organ dysfunction, performance status or ongoing infection.