The nucleic acid synthesis inhibitor decitabine is a commonly used treatment of patients with myelodysplastic syndromes, and also of elderly patients with acute myeloid leukaemia (AML). Despite its widespread use, however, response rates to standard courses of treatment are often low (20–35%). Now, researchers have used enhanced-exome and gene-panel sequencing to identify patients who are most likely to respond to decitabine.

A total of 116 patients with either myelodysplastic syndromes or AML received treatment with a median of two cycles of decitabine. All patients underwent exome sequencing of 264 genes that are known to be recurrently mutated in patients with AML, in addition to amplicon-based panel testing for mutations in eight different genes, followed by array-based analysis of DNA-methylation patterns at day 10 of treatment-cycle one.

Responses to decitabine were more prevalent among patients with unfavourable-risk cytogenetic profiles (67%), which contained virtually all patients with TP53 mutations, compared with 34% of patients with an intermediate-risk, or favourable-risk cytogenetic profile. Furthermore, 100% (21/21) of patients with TP53 mutations responded to decitabine, despite the inferior outcomes associated with having such mutations versus those associated with TP53-wild-type disease. However, despite the highly promising response rates, decitabine did not clear all leukaemia-specific mutations in any of the patients who underwent testing and, therefore, the duration of remission was often limited.

Patients with unfavourable-risk disease had a median overall survival duration of 11.6 months, compared with 10 months in those with favourable-risk, or intermediate-risk disease. Undergoing treatment consolidation with allogeneic stem-cell transplantation was the strongest association with overall survival durations.

These data do not indicate that decitabine is an effective treatment of TP53-mutant AML; however, such an approach could be used to induce remission, if followed by appropriate consolidation therapies.