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Efficacy of Azacitidine in Higher-Risk Myelodysplastic Syndrome (MDS)

Slides from the journal article and transcribed comments from recent interviews with
Gail J Roboz, MD (10/6/09), Steven D Gore, MD (10/8/09) and Hagop M Kantarjian, MD (10/17/09) below

Presentation discussed in this issue:

Fenaux P et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: A randomized, open-label, phase III study. Lancet Oncol 2009;10(3):223-32. Abstract


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GAIL J ROBOZ, MD: This paper is important for clinicians in active practice to read right away. This is the first time that patients with higher-risk myelodysplastic syndrome (MDS) were shown to have a survival benefit with treatment. The azacitidine treatment was compared in an interesting way to three treatments that clinicians would routinely think about using: a low dose of regular chemotherapy, regular induction chemotherapy or supportive care. Azacitidine treatment for these patients increased their survival from a median of 15 months to about 24 months. Patients who might otherwise have been offered supportive care or low-dose ara-C are now receiving azacitidine as standard treatment.

STEVEN D GORE, MD: This is an important paper, probably the most important study that has come out in MDS for some time. Of course, I’m a co-author, so that should be taken into consideration. The study demonstrated a doubling of the two-year survival in the azacitidine-treated group compared to that of the conventional care arm. It established azacitidine at the FDA-approved dose and schedule as the treatment of choice for patients with high-risk MDS.

HAGOP M KANTARJIAN, MD:
This is the first study outside the setting of allogeneic transplant that shows a disease-modifying course in MDS. The study demonstrates that it is not always necessary to achieve a complete response (CR) in order to improve survival. The CR rate with azacitidine in this study was 17 percent, and yet azacitidine was associated with a better median survival. This result may be related to how long you can administer azacitidine therapy to a patient, and since azacitidine is a low-intensity targeted therapy, one could deliver an average of nine cycles in this study. This study also suggests that low-intensity therapy may be better than intensive chemotherapy in some of the more indolent disorders or possibly in elderly acute myelogenous leukemia (AML). A subset analysis of these study data performed by Silverman et al (Blood 2008;112;Abstract 227) looking at the average number of azacitidine courses necessary to achieve a first response demonstrated that about half of the patients that had an initial first response will go on to improve that response with continued azacitidine treatment. This suggests that in MDS, azacitidine treatment should be continued even though a response is not observed after one or two cycles and is in contrast to the ara-C or high-dose ara-C experience in AML. In MDS you may have to persist with your treatment before you see the full response effect.

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 Gore is Professor of Oncology at Johns Hopkins University in Baltimore, Maryland.

Dr Kantarjian is Chairman and Professor of the Leukemia Department at The University of Texas MD Anderson Cancer Center in Houston, Texas.