Studies on the Efficacy and Safety of Deferasirox for Iron Chelation in Patients with MDS: EPIC and US03

GAIL J ROBOZ, MD: These two papers by Gattermann and by List suggest that the agent deferasirox is working as expected. It is removing iron from the blood serum in transfusion-dependent patients with lower-risk myelodysplastic syndromes (MDS). These studies are important because they examine iron chelation in older patients who are on multiple concomitant medications. The initial iron chelation studies were performed in children, which is a completely different patient population.

I believe that iron chelation in MDS is still controversial. There are several important questions that are being addressed by ongoing trials. First, does eliminating iron overload in patients with MDS matter clinically — does it help all patients or only patients at lower risk?

Second, what is the best way to remove iron? There are several iron chelators available currently, but what’s still unknown is what’s the best way to use these agents and could they be combined.

I believe most of us who deal a lot with patients with MDS are struck by the fact that rarely do we seem to see clinical complications from iron overload, especially in patients at higher risk. There seems to be something different going on in these older patients than in children. We don’t know if older patients with MDS are dying from iron overload.

How iron levels should be measured is also controversial. Ferritin levels are easy and convenient to determine, but it is not completely clear if that is the best measurement to use. There are data suggesting that increased ferritin correlates with a poor outcome and decreased survival. But that does not necessarily mean that lowering ferritin levels will increase survival in these patients.

DR LOVE: What is usually the earliest clinical manifestation of iron overload in patients with MDS?

DR ROBOZ: I don’t believe anyone knows that answer. Issues such as endocrinologic and sexual dysfunction are often difficult to detect in older patients. Most oncologists are concerned about cardiomyopathy, but we don’t see much unexplained cardiomyopathy in patients with MDS.

DR LOVE: What are the main downsides of chelation therapy?

DR ROBOZ: Expense is certainly one, in addition to potential interactions with other medications, renal complications, rash and nausea. Chelation therapy is not necessarily an easy treatment to receive as a patient. I would not encourage the random chelation of all patients.

STEVEN D GORE, MD: This treatment for iron overload is already incorporated into clinical practice, though it is not clear that iron overload is a real problem for patients with myelodysplastic syndromes (MDS). Although measurable, ferritin and various parameters associated with iron overload have not been shown to increase cardiac iron or to significantly contribute to mortality in patients with MDS. Most experts believe that it is reasonable to use chelation for patients with low-risk MDS with ongoing transfusion needs. Deferasirox is an effective chelator, but whether chelation should be used or whether it will improve outcomes or survival is uncertain at this point.

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.