New ways to use DNA methyltransferase inhibitors for the treatment of myelodysplastic syndrome.

Ongoing analysis of the seminal AZA-001 study has taught many important lessons in the use of DNA methyltransferase (DNMT) inhibitors. The data emphasize the importance of patience in the use of these drugs, with several cycles required for the manifestations of hematologic responses. Improved survival in patients with high-risk myelodysplastic syndrome (MDS) treated with azacitidine extends to patients with any International Working Group-defined hematologic response; however, the benefit to patients with stable disease is less clear. A great deal remains to be learned about the optimal dosing and scheduling of the DNMT inhibitors, alone and in combination. New information on the impact of DNMT inhibitors on the immune system and on stem cells will likely lead to novel uses of these drugs in MDS and other hematologic and nonhematologic malignancies.