Making the most of hypomethylating agents in myelodysplastic syndrome

Hypomethylating agents (HMA) are the preferred therapy for patients with higher risk myelodysplastic syndromes (MDS) and an alternative therapeutic strategy for older patients with acute myeloid leukemia. These agents have improved both survival and quality of life, but results overall remain poor. The purpose of this review is to highlight recent developments in clinical research with HMA in MDS/acute myeloid leukemia over the last year.

Combination of HMA with B-cell lymphoma-2 inhibitors, hedgehog inhibitors, and a variety of other agents are underway, as are further studies with reformulated HMA that have more favorable pharmacokinetics (including oral bioavailability). HMA may also be promising in maintenance therapy after allogeneic transplantation. Generally speaking, testing new agents in randomized studies after 'HMA failure,' however, may be suboptimal for assessing efficacy.

No clear 'winner' as a combination partner with HMA or novel formulation of HMA has yet emerged. We concur with growing trends to test novel agents early in the drug development timeline, including the frontline treatment setting in combination with HMA, to bring new agents to Food and Drug Administration approval more quickly. HMA are standard in name only, clinical research should be the standard of care.