Myelodysplastic Syndrome (MDS)
Leukemia Insights - Summer 2008
Approved treatments for MDS and CMML include: 1) hypomethylating agents (decitabine, azacitidine) for MDS/CMML; and 2) 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%)
Approaches under investigation include combinations 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%)
To improve the results of hypomethylating agents we are combining them 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), gimatecan (an oral topoisomerase I inhibitor), and other phase I/II agents.