A study presented at the 2013 ASH Annual Meeting focused on the responses seen with oral azacitidine in patients with RAEB-1 or RAEB-2 myelodysplastic syndromes (MDS), notes Harry P. Erba, MD, PhD. The study enrolled 23 patients and administered oral azacitidine primarily at 300mg daily for either 14 or 21 days.

The complete remission (CR) rate was 22% and the overall response rate was 50%, which is similar to other azacitidine administration routes, notes Erba. The rate of marrow CR was 67%, suggesting the possibility to utilize transplant in some patients, Erba notes.

The benefits of oral azacitidine are apparent in the schedule and convenience, Erba believes. At this point, studies have attempted to emulate the same intensity of therapy as other administration routes for azacitidine, resulting in similar side effects, this may be adjusted in future trials, notes Ruben A. Mesa, MD.

Another novel treatment approach involves the utilization of lenalidomide in patients with MDS with 5q deletions. In a phase I/II study presented at the ASH Annual Meeting, lenalidomide combined with intensive chemotherapy was examined in patients with AML and higher risk MDS with 5q deletions. The overall response rate with the combination was 61% with a CR rate of 46%, Erba notes. Additionally, 59% of the patients achieved cytogenetic response. As a result of these promising results, this regimen will move forward in clinical trials, notes Erba.

Another study exploring lenalidomide looked at the agent in combination with azacitidine, notes Erba. Unfortunately, this trial did not demonstrate the same level of results as the phase I/II exploring lenalidomide with intensive chemotherapy. Overall, 43% of patients dropped out of the trial before reaching the second cycle. The overall response rate was 16%.

Ongoing studies are also exploring the combination hypomethylating agents with HDAC inhibitors, notes Elias J. Jabbour, MD. Phase II studies of vorinostat plus azacitidine have shown promise; however, further research is needed to find an optimal combination therapy.