Improving Quality of Life and Survival in Patients with MDS

Transcript:Vinod Pullarkat, MD: The clinical benefit of iron chelation is largely based on retrospective data. Registry studies and other retrospective studies have shown survival benefit for patients who are chelated, and there are retrospective data showing leukemic transformation is delayed in patients who are chelated. So, that could be a major clinical benefit if it is proven in future prospective studies. The other benefit is improvement in hematopoiesis, which can occur in a minority of patients with MDS. They can have a decrease in red cell transfusion dependence, as well as improvement in other counts. The effects on comorbidities, like cardiac dysfunction or endocrine dysfunction, are more difficult to prove without very systematic prospective studies. Overall, I think the most important benefit, potentially, will be improved survival and delayed leukemic transformation.

I have seen improvement in hematopoiesis, sometimes to the point where they become transfusion independent on deferasirox. And, that has now been reported not just in MDS, but in other bone marrow failure conditions like aplastic anemia. That is real and that does occur, and that has major impact on the patient’s quality of life, as well as their long-term outcome.

Heather Leitch, MD, PhD: In MDS patients, regardless of which treatment we use, we always take into account quality of life. In Canada, distance from the treatment center is a very important consideration, and how that will impact on their quality of life. You have to balance the adverse impact of MDS on the quality of life with the potential adverse or positive effects on quality of life of the treatments that are being considered. So, in the case of a patient who becomes transfusion independent with treatment, whether it’s iron chelation therapy or another treatment, it’s very clear to everyone what the impact of the quality of life is on that patient.

In patients with iron overload who don’t achieve transfusion independence, that favorable impact on iron overload may not be as obvious because they may not have symptoms until there’s significant organ damage. We have to factor in a possible adverse impact of side effects of the chelators or other agents against an adverse effect on quality of life, if they develop arrhythmias and congestive heart failure, for example, which I have seen in patients that I’ve inherited once their iron overload is out of control.

I think the best and most dramatic example is for patients who do become transfusion independent with iron chelation therapy. I had a gentleman, early in my practice, whom I inherited 7 years into his diagnosis of lower risk MDS, when he became transfusion dependent. He was requiring three red blood cell units every 4 weeks and had, really, a very poor quality of life in between transfusions as he became more anemic. He would become weaker and short of breath, and described himself as a couch potato. He really wanted to have his transfusions moved to a shorter interval, but his GP, who was managing the transfusions, did not want to do that because he knew about iron overload.

As his ferritin level went up, I offered him iron chelation therapy with deferoxamine, which was the option in Canada at the time. He declined, feeling it would impact further on his quality of life. When deferasirox became available on clinical trial, he reluctantly agreed to try it. And within 6 weeks of starting iron chelation therapy, he received his last transfusion. His hemoglobin improved; it normalized over the coming weeks. It stayed normal for several years until he died in his late 80’s of unrelated causes.

So, he was a very happy camper. He went from couch potato to out building things, gardening, and hunting with his friends. He became the poster boy for iron chelation therapy. As his ferritin came down, I said to him, “We may need to stop this medication so I don’t make you iron deficient.” And, he flatly refused because he was absolutely convinced that it had certainly impacted his quality of life, and also felt that it may have impacted his survival as well, and I have to agree with him.

We also had a second patient, a patient of one my colleagues, who not only became transfusion independent with iron chelation therapy, but, at this point, she was not on clinical trial. She was through our prevention reimbursement. And so, one of the criteria for approval for deferasirox is that the patient is transfusion dependent. She became transfusion independent. When her annual renewal came up, the approval was declined because she was no longer transfusion dependent. Despite that, she remained transfusion independent for 2 years following stopping iron chelation therapy, which she couldn’t afford on her own. I think that the mechanism of this effect is still investigational, but clearly the iron reduction is doing something to the biology of this disease, at least in some patients, that is impacting favorably on their anemia.

Transcript Edited for Clarity