Appropriate Use of Iron Chelators in MDS

Transcript:David P. Steensma, MD: The iron chelators are designed to bind to iron and remove it from the body in ways that are be more efficient than the processes by which the body gets rid of iron anyway. The only way that we have really to get rid of iron, other than by bleeding, is to shed cells from the skin that have a tiny bit of iron in them and shed cells from the gut that have a tiny bit of iron in them. So, that’s very inefficient.

What a chelator does is it binds to the iron and then effectively pulls it out of the body by being excreted in the urine, in the stool, or both, depending on the chelator. So, these chelators can be given by injection. Deferoxamine (Desferal) is the most common one that’s given that way, and that’s been with us for a long time. It’s kind of inconvenient to get injections, and get this every night by a pump, but it is tried-and-true.

Then there are the oral chelators, of which there are two FDA-approved chelators in the United States. But only one is approved for a broad range of conditions, including MDS, and that’s deferasirox, or Exjade—or Jadenu in the new preparation. It’s an oral chelator that binds to iron in a way that seems to be a little bit safer than with deferoxamine, where there’s still a little bit of iron exposed to organisms. Some patients with deferoxamine have had problems with infections that we haven’t seen with deferasirox.

Then there’s a third iron chelator called deferiprone, or L1, that had been used for many years in Canada and Europe, and in the developing world. And this agent is not as potent as deferasirox. The other problem with L1 is that it has about a 1% incidence of agranulocytosis. That is to say, the body stops making white cells, a big problem in MDS obviously. The FDA decided, when they approved this drug a few years ago in the US, we’re only going to approve this for people with thalassemia, or similar inherited disorders who didn’t do well with the other chelators. So, that one really is not applicable in MDS.

There are a wide range of guidelines for chelation, and they differ in many respects. There’s at least a dozen of them. Norbert Gattermann and I have summarized them in several articles. And I think whenever you have a lot of different guidelines with varying recommendations, it highlights that the evidence base isn’t that great for making decisions. Most of the guidelines recommend considering chelation therapy after the patient has had at least 10 to 20 units of red blood cells, the ferritin is over 1000 or over 1500—or over 2000 or over 2500 depending on the guideline—and that the patient has a reasonable life expectancy. So, most explicitly say that for the patient who has higher risk disease, chelation is a side show. It’s a distraction from some of the more pressing concerns, like severe neutropenia and progressive blast increase.

That’s what the guidelines say. In practice, people do a wide variety of things with respect to chelation, and there are some who are very skeptical about chelation. There are other physicians who feel it’s a critical part of the care of the patient with MDS. And most of us are somewhere in between.

In my own practice, what I do is consider chelation in lower-risk red cell transfusion—dependent patients who have some evidence of iron overload besides just a high ferritin. Because, again, high ferritin can be seen in a lot of different states. So I will use an MRI test to help guide which patients are the best candidates for therapy.

I find MRI useful for not only deciding who are the best candidates for chelation, those who have T2* signals that are suggestive of heavy iron overload in an organ, but also you can use it to monitor effectiveness of chelation over time. So, you could do an annual or even an every 2-year MRI to see am I actually chelating effectively or is the ferritin just coming down a little?

Transcript Edited for Clarity