Interview with Thomas Prebet MD, PhD, in advance of the 2015 International MDS Symposium, on topics related to supportive care in MDS and iron chelation therapy.
Thomas Prebet MD, PhD
The proper administration of supportive care can have a significant impact on long-term outcomes, including improvements in overall survival, for patients with myelodysplastic syndrome (MDS), according to Thomas Prebet MD, PhD, the assistant director of myeloid malignancy research at Yale Cancer Center.
OncLive interviewed Prebet, in advance of the 2015 International MDS Symposium, on topics related to supportive care in MDS and iron chelation therapy. Prebet is scheduled to give a presentation on the importance of supportive care during the symposium, which is held from April 29 to May 2 in Washington, DC.Prebet: Most patients with MDS are treated with supportive care, including transfusion, hematopoietic growth factors, and iron chelation therapy. This is the standard of care for the majority of patients with myelodysplastic syndrome.
Basically, supportive care is the basis for any kind of treatment that we want to give to these patients. The way we deal with supportive care could have an impact on survival and quality of life of these patients. Interestingly, it’s not only a quality of life issue but also a survival issue. If you optimize the way you give transplant and if you optimize the way you give hematopoietic growth factors for these patients, you may have an impact on survival.For iron chelation therapy, it’s a hot topic in the field of MDS. Basically, any patient who needs chronic transfusions may need to be chelated. We know that patients with transfusion dependency will develop iron overload, and will usually have a worse outcome. We know from different studies that the correction of this iron overload can reverse this and improve outcomes.
We need to be careful with what we call supportive care because most of the methods that we have may have some impact on the patient’s outcome. Supportive care is more than supportive in this group of patients, especially when it comes to transfusions.Chelation is a supportive care method that should be synced with objectives. Usually, we use chelation therapy for patients who have been transfused with more than 20 units of red cell over the period of a few months or a few years. Some criteria for ferritin levels can be debated.
The situation can be different for a patient who is younger—whom you think might be good for transplantation—who you want to optimize for transplantation. You may overload with transfusions, needing chelation. On the other end, if you have an older patient above 95 years, you may not need to go to chelation. You should consider the risks and benefits.
The next question facing this process is treatment selection. There are two agents approved for iron chelation: deferoxamine, which is administered intravenously and subcutaneously, and can be really complicated form a logistic point of view and can be associated with side effects. The second approach is, deferasirox, which recently had a new oral formulation approved.
This agent is easier to handle compared with infusions every day, which was the basis with deferoxamine. It was associated with some important side effects; it could lead to transient renal blockade, serial diarrhea, and some other side effects. It is a good medication and is easier to handle than deferoxamine. It's something you need to monitor quite severely in the first month of treatment and try to adapt the way you are giving the drug.
There can be such a big focus on the treatment aspect—which agent they are receiving, lenalidomide or some other treatment—that side effects can be overlooked. There needs to be education on the supportive care aspect as well. Education on chelation therapy is important.The new formulation is easier in the sense that it’s just a pill as compared to the former formulation that was a kind of syrup to drink. The new formulation also comes with fewer gastrointestinal side effects and the efficacy seems to be at least equivalent.
One of the things that’s important is if you look at the last clinical trial of Exjade, for example, most of the patients don’t have six months of treatment because they have to stop treatment due to side effects. One of the findings from these studies is that, the better the patient is chelated, the better the outcome is. So if this new formulation improves tolerance and compliance to the treatment, we may even have a better efficacy of the treatment and better outcome. But this still needs to be proved.
The trend for the moment, at least what is expected or logical, is that this new formulation will result in better compliance and better efficacy for patients. I think the most important thing is that MDS should be considered a chronic disease. It’s sometimes hard to keep focus on all the aspects, especially transfusions. It’s patients that you see every week or every two weeks for more than 6 months, and we need to be aware and reactive and, in some cases, proactive in order to avoid the complications that can come with transfusions and to try to improve the quality of life of these patients.
Medications that we’re using for supportive care can still have some side effects so we need to follow up with these patients, especially in the first month of treatment.There are two groups of patients: those with low risk MDS and those with high risk MDS. Patients with low-risk MDS have a low risk of progression to acute myeloid leukemia. These patients are the ones with long follow-ups over multiple years and for which we have these issues of dealing with long-term treatments and long-term transfusions. In this group of patients, the objective will be to optimize quality of life.
One of the challenges here is that for moment we don’t have any curative treatments, except bone marrow transplantation. And this is only applicable to a minority of patients, for multiple factors, but also since the average age of patients is 70 years.
Another challenge is focused on the other group of patients, which are those with high-risk MDS, or those that are likely to progress to leukemia. These patients have short survival. If you don’t treat them, the survival will be around 15 to 20 months. With treatment, you can go to a median survival of 2 years.
We have tried to have effective treatments with this group of patients. But even for patients that have response with treatment, we are still dealing with the issue that we don’t have any definitive treatment. We know that at one point or another, patients will relapse or progress.