A clear connection between response to hypomethylating agents (HMAs) and distinct genetic markers has yet to be established for patients with myelodysplastic syndrome (MDS). Mutations involved in DNA methylation have shown promise for predicting response to azacitidine, including TET2 and EZH2 mutations. However, these aberrations do not provide a high-level of certainty regarding who will or will not response, states Rafael Bejar, MD, PhD.

Small subsets of patients with MDS acquire FLT3-ITD mutations which accelerate AML transformation, states Elias J. Jabbour, MD. These mutations are being investigated as the target for novel therapies currently in development, such as quizartinib. The acquisition of a mutation like FLT3-ITD may predict aggressive disease and transformation to AML, Jabbour believes.

Studies have explored the impact of achieving a complete cytogenetic response (CCyR) on outcomes for patients with MDS treated with HMAs, notes Jabbour. In one such analysis, CCyR correlated with better long-term outcomes, regardless of morphologic response. CCyR occurred at a rate of 31% in patients with MDS treated with HMAs. The 2-year overall survival for those achieving CCyR was 20 months compared with 14 months without.

These findings suggests that CCyR should be added to morphology for assessing response to therapy, since MDS is not a static disease, says Mark J. Levis, MD, PhD. The addition of cytogenetic or molecular monitoring in MDS could facilitate the decision to undergo transplantation, suggests Ruben A. Mesa, MD. Additionally, it could help provide a clear picture of the overall prognosis for patients.