There are currently three therapies approved for the treatment of patients with myelodysplastic syndromes (MDS): azacitidine, decitabine, and lenalidomide. Azacitidine is approved for patients with all FAB subtypes of MDS, including acute myeloid leukemia, notes Harry P. Erba, MD, PhD. In clinical trials, the median survival with azacitidine was 24.5 months versus 15 months with conventional care regimens. Additionally, the FDA has approved decitabine for all FAB subtypes and intermediate-1, -2, and high-risk IPSS groups of MDS. This approval was based on an improvement in overall response rates compared with supportive care.

The oral agent lenalidomide is FDA-approved for the treatment of low and intermediate 1 risk transfusion-dependent patients with MDS who harbor a del5q cytogenetic abnormality. In phase III studies, transfusion independence lasting longer than 6 months occurred in 43% to 52% of patients treated with lenalidomide.

Clinical trials continue to assess possible new therapeutics for patients with MDS, Erba notes. Early studies showed promise for combined treatment with lenalidomide and epoetin alfa for low-risk patients with MDS refractory to erythropoiesis-stimulating agents, notes Rami S. Komrokji, MD. The response rate with the combination was near 20% for patients who did not previously respond to single-agent lenalidomide, Komrokji notes. Furthermore, these responses were seen in patients with non-del5q MDS, representing a potential new treatment options. Phase III studies are underway to further examine this approach (NCT00843882).

Combination strategies are the focus of several ongoing studies attempting to find new treatments for patients with MDS. In phase I and II studies, the combination of lenalidomide and azacitidine for high-risk patients with MDS demonstrated promise. These studies established the combination as well tolerated and highly active, warranting further investigation, Erba notes.

The combination of the HDAC inhibitor vorinostat and azacitidine has also been explored as a treatment for patients with MDS, notes Erba. In earlier-stage trial, this combination was shown to be safe and effective. The future for these experimental regimens will be determine by the results of larger trials.