Management of Myelodysplastic Syndromes: A Focus on Supportive Care - Episode 14

Iron Chelation Therapy Efficacy and Safety in MDS

Transcript:James M. Foran, MD, FRCPC: What is the role of the patient in deciding on iron chelation therapy? There are two oral chelating agents—a third one that’s approved in a different setting, deferiprone—and then there’s Desferal, or deferoxamine, that’s the subcutaneous. What’s the role of the patient in deciding deferasirox, or deferiprone, or Desferal? Is that a discussion that you have with the patients?

Azra Raza, MD: I do have a discussion with the patients. I do describe to them the possibilities that are available, and 99% of them want to depend on my judgment, and my experience, and observations with other patients. And, I’ll give them the benefit of my experience and tell them that I think an oral agent is the best way to go. Amongst the oral agents, one of them can reduce the blood count, so we don’t want to take that risk. Then we have really two choices left out of those two oral choices. The one that is more palatable and easier to tolerate is the newest one. And, so, we have these discussions about various possibilities.

James M. Foran, MD, FRCPC: I like that you have a discussion about that to educate them as to why they’re going through it. And, I think you’re lucky if 99% of your patients agree with you and defer to you because that’s a higher percentage than my practice. But, it makes sense to me also. We had a lot of experience with deferasirox with the Exjade formulation and found that we had to make a lot of dose adjustments, or start at lower dose, or sometimes chelate less than optimally just to get people to tolerate it from the gastrointestinal toxicity, still monitoring for nephrotoxicity or retinal toxicities. But, the newer formulation I think is sort of a remarkable thing, that they’re willing to take the same drug, change the formulation just to make it more tolerable, is an important advance and at least will deal with some of the side effects for people with gastrointestinal (GI) toxicity. I’m thinking about your patient, and the endocrinologist who ended up having him on both subcutaneous and oral chelation. And, rarely, we’ve been in that situation as well, where we really needed to address iron overload and had to be more aggressive to do it for tolerance, one or the other. That’s an unusual situation but that definitely happens.

Azra Raza, MD: You know, another thing, James, I have suggested is that we should have testimonials from real patients who have been on iron chelation therapy, for whom it has made a big difference that they’re getting transfusions. I have a patient literally who I’ve been treating for 20 years. For the last 11 years, she has been transfusion-dependent, at least3, sometimes 6 units a month. That’s a heavily transfusion-dependent patient for 11 years. She was just in the Amazon jungle. She is traveling all over, gallivanting the globe, going out to dinners. Why? Because she’s so aggressive in her iron chelation, her ferritin level is never over 800. If it goes to 801, I get 4 calls from her saying, am I going to die because my ferritin is going up? But she’s able to take the transfusion safely because she is so vigilant. And a testimonial from a patient like that would be so encouraging to those patients who are having second thoughts about it and saying, ‘I don’t want to do it.’

James M. Foran, MD, FRCPC: Well, there is nihilism in our field. If we can’t prove in a randomized study that some intervention made a difference in survival, or a hard endpoint, then people don’t really want to do it if it has any expense or any toxicity. But I agree with you, that’s a really important point. If you’re in a practice that doesn’t have a lot of MDS patients, you may not see somebody who you’re starting chelation on and they improve their cytopenias. And that’s a real thing where you start chelation, you can see improvement of underlying hematopoiesis. I don’t think the mechanism is completely worked up but it must be involved with some of the things you were mentioning. But you won’t pick that up in a practice where you don’t have a large enough group of MDS patients, and therefore it feels anecdotal. So, I hope that we’ll be able to package those experiences in a way where people can see the impact of the intervention.

Azra Raza, MD: Excellent point. Thank you.

James M. Foran, MD, FRCPC: I wanted to discuss what success looks like when you’re dealing with chelation. What are you monitoring, or what do you say was the success for the patient? We don’t take holidays from chelation like you do, although that makes sense as a practice. But, how do you decide to do that?

Azra Raza, MD: I think when you see the ferritin level is now below 500, then, most of it is really from the disturbed iron metabolism, due to ineffective hematopoiesis. Especially if you have the baseline before transfusions—ferritin level—and you see that you’ve reduced it down to that level again, then I really think it’s important to give a break to the patient. Success to me is measured by a steady reduction of the ferritin level to below 500. Secondly, improvement of cardiac and liver function if that was affected to begin with. Third, improvement in cytopenias when they are getting no disease-modifying drugs. This could be attributed to nothing else but aggressive chelation therapy. So, all those are indications of success of the therapy.

James M. Foran, MD, FRCPC: We would follow a very similar practice. If we can get the ferritin down to less than 500, we’d be happy. In hemochromatosis, for instance, we’re trying to target a ferritin of 50 or 35, and that’s a different setting. That may not be realistic here, not to say we shouldn’t try that. I just don’t have that experience.

Azra Raza, MD: No, it isn’t realistic because most of the high ferritin is from ineffective hematopoiesis. It is not a true iron overload.

James M. Foran, MD, FRCPC: Well, that’s a good point. It’s a more complicated pathophysiology, isn’t it?

Azra Raza, MD: Yes.

James M. Foran, MD, FRCPC: Yes. And, so, how do you monitor prospectively for side effects or for toxicities in somebody who you’re chelating? So you’re monitoring their ferritin every, I don’t know how often you do that actually.

Azra Raza, MD: We do it once a month.

James M. Foran, MD, FRCPC: Monthly, okay. So that’s a little more frequent than other practices. You’re dogged about it. And, how do you monitor for toxicities, are you checking renal function from time to time? Do you have your patients see an ophthalmologist from time to time?

Azra Raza, MD: All of the above, yes.

James M. Foran, MD, FRCPC: Yes. Well, that makes sense. And I think that will be an important point with the newer formulations because ironically, adherence will improve. And, therefore, we’ll have to be as aware or more aware of toxicity as patients are able to stay on the medications who couldn’t tolerate from before from GI side effects.

Transcript Edited for Clarity