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TP53 Mutations in Leukemia and MDS Respond Well to Dacogen

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Patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) who have genetic mutations, including the TP53 mutation, that typically result in poor outcomes, respond well to the agent Dacogen (decitabine). These results were recently published in the New England Journal of Medicine.

Both AML and MDS are diseases that affect blood cells. AML is a fast-growing type of leukemia, and MDS is sometimes referred to as a pre-cursor to cancer, as it can remain slow-growing for an extended period of time. However, MDS carries the potential to turn into an aggressive leukemia, and is therefore often treated.

Many types of cancers are now being evaluated for different genetic abnormalities, as these differences often reflect responses to treatment, and long-term outcomes. Understanding the roles that these different genetic abnormalities play in particular diseases ultimately allows healthcare providers to individualize treatment options for optimal care of each patient.

Some known genetic abnormalities exist that can be tested for in AML and MDS. These genetic abnormalities are associated with different long-term survival outcomes among patients treated with conventional chemotherapy.
Patients with genetic abnormalities that tend to confer in shorter survival times are referred to as having an unfavorable-risk cytogenetic profile, while those associated with a greater long-term survival are referred to as having a favorable-risk cytogenetic profile. Researchers are just beginning to identify and understand these different genetic abnormalities in AML and MDS, and extensive research is ongoing in an attempt to gain a better understanding of this issue.

Researchers recently evaluated patients with MDS and AML with different-risk cytogenetic profiles. The study included 116 adult patients who were tested for genetic abnormalities, and were treated for 10 days with the agent decitabine. One aim of the study was to determine the associations between the different cytogenetic profiles and their responses to treatment with decitabine, which is an agent approved for the treatment of both MDS and AML.

• Patients with an unfavorable-risk cytogenetic profile had improved responses to decitabine, than those with an intermediate- or favorable-risk cytogenetic profile. Anti-cancer repsonses were achieved in 67% of patients with an unfavorable-risk profile, and only 34% of those with an intermediate and favorable-risk profile.

• 100% of patients with the TP53 mutation had an anti-cancer response to decitabine, compared with only 41% of those who did not have a TP53 mutation.

• Patients with unfavorable-risk cytogenetic profiles, including the TP53 mutation, did not have a worse overall survival than those with intermediate-risk profiles.

The researchers concluded that among patients with AML and MDS with an unfavorable-risk cytogenetic profile, and those with the TP53 mutation, treatment with decitabine is associated with high rates of anti-cancer responses, resulting in similar overall survival to those with intermediate-risk cytogenetic profiles.

Reference: Welch J, Petti A, Miller C, et al. TP53 and decitabine in acute myeloid leukemia and myelodysplastic syndromes. New England Journal of Medicine. 2016; 375:2023-2036.