Myelodysplastic Syndrome (MDS)
Leukemia Insights - Spring 2007
Current approved strategies in MDS and CMML include the use of hypomethylating agents (decitabine, azacitidine) for MDS/CMML, and the use of lenalidomide (a thalidomide analog) for low risk MDS transfusion dependence and 5q abnormality. We are investigating several strategies to improve the results beyond the standard of care. These are based on the IPSS/general risk of the MDS.
Lower risk MDS (IPSS low – intermediate-1; blasts < 10%)
In lower risk MDS we are investigating several approaches including combination of growth factors, immune therapy (rabbit ATG), GX15070 (a Bcl 2 inhibitor shown to stimulate multilineage hematopoiesis), vorinostat (a histone deacetylase inhibitor shown also to stimulate multilineage hematopoiesis), and low doses of decitabine – azacitidine. In lower risk MDS as well as higher risk MDS with 5q abnormality, lenalidomide based regimens are under investigation.
Higher risk MDS (IPSS intermediate-2 – high; blasts > 10%)
We are attempting to improve the results of hypomethylating agents using them in combination with histone deacetylase inhibitors. Programs in these MDS subtypes include decitabine + valproic acid, decitabine + vorinostat, azacitidine + MGCD.
For patients who fail on hypomethylating strategies, investigational strategies include clofarabine, PO and IV, sapacitabine (an oral cytosine analog), homoharringtonine, gimatecan (an oral topoisomerase I inhibitor) and other phase I/II agents.