A serial 10-day course of decitabine induced favorable clinical responses and robust, but incomplete, mutation clearance among patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) who harbored TP53 mutations, cytogenetic abnormalities associated with unfavorable risk, or both, according to a study published in The New England Journal of Medicine.1

Decitabine is a nucleoside metabolic inhibitor approved by the U.S. Food and Drug Administration for the treatment of patients with MDS and is often used off-label for patients with AML. The molecular determinants of clinical response to decitabine therapy, however, remain unclear.

To identify somatic mutations and their relationships with clinical response, researchers enrolled 84 adult patients with AML or MDS in a single-institution study. All patients received decitabine daily for 10 consecutive days in monthly cycles.

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Researchers performed enhanced exome or gene-panel sequencing in 67 of these patients and serial sequencing at various time points to assess patterns of mutation clearance in 54 patients. In an extension cohort, investigators included 32 additional patients who received decitabine in different protocols.

Results showed that 67% of the 43 patients with an unfavorable-risk cytogenetic profile achieved a clinical response compared with 34% of the 71 patients an intermediate-risk or favorable-risk cytogenetic profile (P < .001).

In addition, 100% of the 21 patients with TP53 mutations had a response vs 41% of the 78 patients with wild-type TP53 (P < .001).

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Although these responses were not durable, researchers found that overall survival rates were similar to those of patients with AML who had an intermediate-risk cytogenetic profile and who also received serial 10-day courses of decitabine.

Previously reported studies have consistently demonstrated that patients with an unfavorable-risk cytogenetic profile and TP53 mutations who receive conventional chemotherapy have poor outcomes. But this study of 10-day courses of decitabine suggested that neither of these risk factors was associated with worse overall survival than that of patients harboring intermediate-risk cytogenetic profiles.


  1. Welch JS, Petti AA, Miller CA, et al. TP53 and decitabine in acute myeloid leukemia and myelodysplastic syndromes. N Engl J Med. 2016;375:2023-36. doi: 10.1056/NEJMoa1605949