Phase II Study of Maintenance Treatment with 5-Azacitidine for Patients with MDS or Post-MDS AML
Slides from a presentation at ASH 2008 and transcribed comments from interviews with Gail J Roboz, MD (10/6/09) and David P Steensma, MD (12/18/08)
Presentation discussed in this issue:
Grövdal M et al. Maintenance treatment with 5-azacitidine for patients with high risk myelodysplastic syndrome (MDS) or acute myeloid leukemia following MDS (MDS-AML) in complete remission (CR) after induction chemotherapy. Blood 2008;112;Abstract 223.
GAIL J ROBOZ, MD: Currently there is no known role for maintenance therapy in acute myeloid leukemia (AML). I believe this study is important because in addition to scientific rationale, the study demonstrated that it is feasible to consider azacitidine for patients with AML who are in remission. The dosing of azacitidine in maintenance for AML may be different than the approved dose for myelodysplastic syndromes. Larger cooperative group studies are ongoing and will help clarify the role of 5-azacitidine in maintenance therapy.
DAVID P STEENSMA, MD: This study addressed the common problem in MDS and in post-MDS AML of the relapse rate being very high for patients who achieve a remission. The availability now of hypomethylating agents such as azacitidine and decitabine has led to the question of whether these drugs could be used as part of a maintenance program to help keep patients in remission.
This study followed patients with high-risk MDS or post-MDS AML who were ineligible for transplant. They received a standard leukemia-like induction regimen, and the patients who achieved complete remission (CR) were maintained with a low-dose azacitidine regimen. It is hard to say what the meaning of the results are without a control arm, but I believe that it is slightly sobering that most of the patients experienced relapse and that the median CR duration was only 13.5 months. That result is within the realm of what one might expect with just induction alone in this group, perhaps slightly longer, but it is difficult to say.
The study did, however, examine the promoter methylation status of three different genes, and hypermethylation of E-cadherin was associated with a poor overall survival (three months) compared to those in whom the gene was not hypermethylated at baseline. No consistency was seen between methylation and durability of response or changes in methylation and outcome. This issue of how to maintain remissions still warrants further investigation.
Dr Roboz is Associate Professor of Medicine and Director of the Leukemia Program at Weill Medical College of Cornell University at NewYork-Presbyterian Hospital in New York, New York.
Dr Steensma is Attending Physician at Dana-Farber Cancer Institute and Associate Professor of Medicine at Harvard Medical School in Boston, Massachusetts.