Global Expert Perspectives on Managing Excess Iron - Episode 11
Transcript:Thomas Prebet, MD, PhD: When we talk about giving iron chelation agents, most of the patients now are started on deferasirox, which is the oral formulation. There are two available options. One is pills, Jadenu; it’s a newer formulation. The other one is Exjade, and it has been used for years now. Most common side effects that we have with deferasirox, which is the active molecule in both of these medications, are basically some gastrointestinal side effects. That’s the first thing that we need to face, especially with Exjade. There are some potential kidney issues, especially at the beginning of the treatment. Also, liver function test abnormalities and transaminitis are pretty common because of the formulation.
One of the things that we need to face on a common day-to-day basis with these agents is to find good levels and the good dose of the agents. It can be pretty complicated to find a balance between side effects and the efficacy to begin to get treated of the excess of iron. But with the new formulation of deferasirox, or Jadenu, potentially you can get rid of some of the gastrointestinal side effects. If we have a better look at the toxicity profile, potentially we can give to the patients more of the drug and have a better efficacy for this patient to be able to reach the goals of treatment that we have, basically based on ferritin levels.
From the patient perspective, the liver function test abnormalities are maybe not the most common concern. With the use of Exjade, it was complicated for the patients, and almost a ritual every morning, to dissolve the Exjade in a big glass in order to take the medication. While with the new medication that we have, the new formulation of Jadenu, it’s much more convenient for the patient because we don’t have all of this preparation and day-to-day basis ritual. So, it’s much more convenient for the patients to have Exjade, in particular.
Heather Leitch, MD, PhD: In terms of quality of evidence regarding iron chelation therapy in MDS, we’d like to have data from randomized, controlled, placebo-controlled trials. We’d like to have that for everything we do in medicine. Unfortunately, we do not yet have the results of the TELESTO trial, which is the phase III randomized, placebo-controlled trial comparing deferasirox to placebo. The results are expected within the next couple of years. But I think that we have a lot of not only clinical indications, such as the transfusion independence, but also preclinical data that demonstrates that iron overload is deleterious and that reducing iron overload, whether it’s with chelation or whether it’s with phlebotomy in transfusion-independent patients, is beneficial. I also think that we need to keep in mind that we just don’t have phase III clinical trial for everything we do in medicine. For example, it’s only just now that randomized, controlled trial data for the use of erythropoiesis-stimulating agents in MDS is becoming available. And yet, this has been the standard of care for many years in MDS.
It’s our impression that a lot of the issues with adherence with Exjade, the dispersible formulation, are related to GI intolerance. So, based on the experience of our United States colleagues, and these data are still early, the adherence is better with the new formulation, Jadenu. At 3 months of chelation, adherence is improved to 70% from 60% with Exjade.
In terms of switching patients over to Jadenu, or starting them on Jadenu—patients who haven’t been on iron chelation therapy before—it’s important to remember that pharmacokinetic data show that not as much of a dose of Jadenu is required as Exjade to achieve the same chelation effect. So, when switching patients over, basically it’s recommended to lower the dose by 30%. Some of my colleagues have actually recommended lowering the dose initially by 50%. The reason for this is that with the dispersible formula with Exjade, you can get a slurry in the bottom of the glass. And so, maybe not all the Exjade is actually being ingested. By decreasing by 50% to start with, then you won’t run into sudden surprises in terms of creatinine levels and so on.
Transcript Edited for Clarity