Mutation-Driven Therapy in MDS

Genetic sequencing in myelodysplastic syndrome (MDS) has provided an improved understanding of the complexity and heterozygosity of the disease. More importantly, our molecular understanding of MDS is leading to rapid advancements and personalized therapy for our patients. Herein, we review the current mutation-driven treatment landscape in MDS, first focusing on individual mutations. We then discuss the effect of specific gene mutations on response and outcomes to standard therapies as well as to cutting edge investigational therapies.

Molecular annotation of MDS can predict response rates and outcomes to our current standard of care therapies including hypomethylating agents, lenalidomide, and allogeneic stem cell transplantation. Clinical trials targeting molecular subsets of MDS are underway with some in very early stages while others advancing to phase III trials. Targeting TP53 and IDH1/2 mutations appear to be promising targets with substantial efficacy seen in several trials to date. Furthermore, novel therapeutic strategies such as immuno-oncology agents are of significant interest with future investigation required to understand the molecular predictors of response. Mutation-driven therapy in MDS is rapidly expanding and has tremendous potential in a disease where limited standard therapy options exist.