The Clinical Value of Decitabine Monotherapy in Patients with Acute Myeloid Leukemia.

Decitabine (5-aza-2'-deoxycytidine) is a hypomethylating agent used in the treatment of acute myeloid leukemia (AML). Decitabine inhibits DNA methyltransferases, causing DNA hypomethylation, and leading amongst others to re-expression of silenced tumor suppressor genes. Decitabine is indicated for the treatment of adult patients with newly diagnosed de novo or secondary AML who are not eligible for standard induction chemotherapy. The initial authorization in 2012 was based on the results of the open-label, randomized, multicenter phase 3 DACO-016 trial, and supported by data from the supportive phase 2 open-label DACO-017 trial. Compared with standard care, decitabine significantly improved overall survival, event-free survival, progression-free survival, and response rate. Decitabine was generally well tolerated, offering a valuable treatment option in patients with AML irrespective of age, especially for patients achieving a complete response. Several observational "real-life" studies confirmed these results. In contrast to standard chemotherapy, the presence of adverse-risk karyotypes or TP53 mutations does not negatively impact sensitivity to hypomethylating therapy albeit with lower durability. Data suggest a potential positive effect of decitabine in patients with monosomal karyotype-positive AML. For the time being, decitabine is an appropriate option as monotherapy for patients with AML who are unfit to receive more intensive combination therapies, but emerging data suggest that decitabine-based doublet or triplet combinations may be future treatment options for patients with AML.