The Role of Iron Chelation Therapy in Patients with MDS

Transcript:James M. Foran, MD, FRCPC: What about for patients who are going for transplant? I heard you say earlier that’s an evolving discussion and you’re thinking of it at multiple times during their punctuated equilibrium. Does iron overload, or iron chelation, play into your transplant discussion or your transplant plan for patients?

Azra Raza, MD: Actually, surprisingly not just iron overload, but the level of iron overload can determine post-transplant survival. So pre-transplant ferritin level has been significantly correlated with post-transplant survival. Therefore, it is very important that if the ferritin level is below 2500 or above 2500 before transplant, it has a significant effect. It is incumbent upon us to make sure that we bring down the ferritin level prior to transplant. Now, many people can say, oh, their ferritin level is high only because their disease is worse and they’ve been getting lots of transfusions. Yes, all that is possible, but at least it’s something you can do a little bit about. So why not give the patient the benefit of that doubt and go ahead and aggressively reduce their ferritin level anyway?

James M. Foran, MD, FRCPC: Biologically, I agree. It’s also plausible. It facilitates opportunistic infection or fungal infection, and that’s a cause of morbidity and mortality after transplant. I think one of the problems is, that at a center like yours or mine, where the coordination of care pre-transplant and post-transplant is closer, for somebody who’s managing a patient who is not in a transplant center and sending them for a transplant referral, there may not be that communication about the importance of chelation. I think that the transplant physicians may be able to play a role when they’re evaluating patients to say, by the way, we’d really like their ferritin to be less than 2500, and even less than 1500 to try to improve our outcomes. So, that as somebody goes through their induction with azacitidine, for instance, or someone who’s on a trial or whatever medicine you’re using, as you’re planning transplant, that gets incorporated into thinking earlier on. And I think it’s a way to try to improve our late outcomes. I don’t know if it would work, but see if we can’t improve that survival after transplant and try to raise it up above 40% or 50%. That’s an area where we may be able to impact.

Azra Raza, MD: And my three points in answer to that is for everyone. What we need is education, education, education. We have to make everyone aware that this is a serious issue. I think for far too long, James, these kinds of things have been ignored because we are running after trying to cure the disease. I always say, what other diseases have we really cured besides infectious diseases, some of them? We haven’t cured really any neurologic disease, any cardiac disease unless you have some surgical intervention, or any of the chronic endocrine diseases. Why are we trying to cure cancer? We can convert it into something patients can live with as long as improve their quality of life and make it into a chronic disease that they don’t die from. And I think in making it a chronic disease, the most important thing is the quality of life and you can improve the quality of life by these measures. And this why education is so important.

James M. Foran, MD, FRCPC: I think that’s going to be a helpful point for people in practice who struggle with this issue. It can help them have a long-term view or a longitudinal view of what will happen for that person they’re treating or those people they’re treating, and then to be able to plan things like chelation if they think it’s appropriate to try to get better long-term outcomes. They can try to convert it into a long-term problem rather than a short-term acute decision. Medicine is somewhat disjointed at the moment or fractured, but I think our practices have the ability do that, and that’s a consideration. Just speaking functionally then, what are your recommendations or what’s your practice for actually monitoring patients prospectively and intervening with iron overload?

Azra Raza, MD: I think it’s very important, first of all, for the treating hematologist to be very vigilant about following the ferritin levels of patients, especially those who are transfusion-dependent. And my recommendation is that the sooner we start chelating patients, the better the results. Once a patient has received 10 transfusions or 20 units of blood, and if their ferritin level is over 1,000, you start having serious discussions and educate the patient about how much they can do to help themselves. Yes, this is not the most palatable treatment. People have dyspepsia, some GI disturbances. We have to watch out for other side effects of these drugs. No drug is without side effects, but the important thing is, is the benefit worth the risk? And in this particular scenario, hematologists are the ones. It is incumbent upon them to talk to the patients and explain to them what the risks are and what the benefits we are expecting are.

As soon as that threshold of a certain number of transfusions and a ferritin level is reached, we start having the conversation. We start the patient on chelation therapy. You don’t have to start at the highest dose if you think patient has comorbidities and other issues. Start at a lower dose and work your way up as the patient develops tolerance. And just follow their liver function, their renal function, and their GI function carefully. And then titrate the drug up or down as needed. Even intermittent chelation is better. So, if you start earlier, the ferritin level of 1,000, bring it down to 500 or below and stop. But if they continue to get transfusions, this level will come up again over the next 6 months to a year. Once it comes to 1,000, you again institute chelation therapy. So, in other words, if you start early, you’ll end up having intermittent chelation just by your vigilance.

James M. Foran, MD, FRCPC: Sometimes it gets thought of as just a supportive care measure and so it gets swept aside because we say, well, we’re focusing on the disease with azacitidine, but we’re not actually. And then supportive care is worrying about iron, or nausea, or their transfusion level, or when to actually give them blood. But I really like your point about transfusing safely and I liked your point about trying to educate the patient about it, and I think those are really critical things.

Transcript Edited for Clarity