Decitabine an option for select AML, MDS patients
medwireNews: Adult patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) who have an unfavorable-risk cytogenetic profile or harbor TP53 mutations could benefit from treatment with decitabine, indicate findings.
The study included 84 participants given decitabine 20 mg/m2 per day on the first 10 days of a 28-day cycle, and an additional 32 patients formed an extension cohort, of whom 24 received the same 10-day regimen while eight received decitabine at the same dose but for only 5 days in each cycle.
Nearly half (46%) of the 116 patients achieved bone marrow blast clearance, defined as less than 5% blast cells, the team reports in The New England Journal of Medicine.
However, significantly more participants with an unfavorable-risk cytogenetic profile achieved a response than their counterparts with an intermediate- or favorable-risk profile, at 67% of 43 versus 34% of 71 patients.
Similarly, all 21 patients with TP53 mutations responded to decitabine treatment, compared with less than half (41%) of 78 participants with wild-type TP53, a significant difference.
“These outcomes contrast sharply with those in patients with AML who receive standard anthracycline-based and cytarabine-based induction chemotherapy, in whom the presence of TP53 mutations is associated with a dismal prognosis, with initial response rates of only 20 to 30%,” say Timothy Ley (Washington University School of Medicine, St Louis, Missouri, USA) and fellow investigators.
Furthermore, a post hoc analysis showed that neither risk factor adversely affected overall survival (OS) in the context of decitabine treatment. Median OS durations were comparable between patients with unfavorable-risk and those with intermediate- or favorable-risk, at 11.6 versus 10.0 months, and also among those with and without TP53 mutations, at 12.7 and 15.4 months, respectively.
Ley at al comment: “These data suggest that the poor prognosis associated with an unfavorable-risk cytogenetic profile, the presence of TP53 mutations, or both may be specific for the treatment approach and may be mitigated with decitabine therapy.”
In a related editorial, Elihu Estey (University of Washington Medical Center, Seattle, USA) points out that the authors’ definition of response was quite broad, encompassing not just complete remission, but also complete remission with incomplete count recovery and morphologic complete remission. He notes that only four of the 21 patients with TP53 mutations achieved clinical remission.
Nonetheless, “the diverse molecular architecture (and brief remissions) observed in this trial” calls into question the current policy of regarding AML as a single disease and targeting it with a single drug, Estey observes.
He concludes that the study “points to inevitable, rational replacement of large trials in which homogeneous therapy is administered for a heterogeneous disease by smaller, subgroup-specific trials.”
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