Iron Chelation Therapy in MDS: A Look at the Evidence

Transcript:David P. Steensma, MD: We know in thalassemia that chelation therapy prolongs life. There are several studies about adequacy of chelation correlating with survival. And although there might be some confounding factors there, it seems chelation is critical for patients with congenital anemias. In MDS, we know that the chelators can lower iron, they can lower ferritin, and they can lower other parameters such as the labile plasma iron—which is a non-transparent bound volatile iron species. But we don’t yet know that chelated patients are necessarily going to do better because of the chelation. What we’d like to know is that by chelating the patient, we can prevent organ complications, we can prevent death from cirrhosis, or cardiomyopathy, or bone marrow complications that could relate to iron. But, we don’t know that yet. We don’t have prospective controlled data to suggest that chelation is beneficial. It’s all either phase II trials where there was no comparator or retrospective studies.

TELESTO is an important study because it is a prospective randomized trial of patients who are at lower risk MDS and are transfusion-dependent, transfusion requiring. It is placebo-controlled so that one can get a clear picture of both toxicity and potential benefits of the chelating agent in this population. The problem with TELESTO is that it had originally been envisioned to be a much larger study than what it turned out to be. It’s now medical. And observation of the patients is continuing, and they’re counting events and seeing which does better.

But the sponsor found it very difficult to enroll to TELESTO because a lot of physicians had already made up their mind, and because the patient criteria were very, very narrow. You had to be transfusion-dependent enough that somebody was concerned about iron, and yet have a quite low risk disease such that you could potentially be monitored for 3 to 5 years for the study. And that’s a fairly small fraction of patients of MDS that have fit into that category.

So, I hope TELESTO gives us a useful result. I hope it’s positive. It would be great to know there’s something else that we can do to help improve our patient’s outcomes. But I’m somewhat skeptical that it’s going to resolve the question.

Transcript Edited for Clarity