Transcript:James M. Foran, MD, FRCPC: Hello, and thank you for joining this OncLive Peer Exchange. Supportive care for myelodysplastic syndromes often involves regular blood transfusion support, which can lead to progressive accumulation of iron and iron overload. Although prospective data are lacking, retrospective studies and meta-analyses have shown that excessive iron levels are associated with significant morbidity and mortality in patients with MDS. This OncLive Peer Exchange will provide a background on MDS disease characteristics, and supportive care, and will discuss the role that iron chelation therapy plays in the management of iron overload.

My name is Dr. James Foran. I’m an associate professor of medicine, and also associate chair of medicine for research in the Division of Hematology and Medical Oncology at the Mayo Clinic Cancer Center in the Mayo Clinic, Florida. Today, I’m joined by Dr. Azra Raza, professor of medicine and director of the MDS Center at Columbia University Medical Center. And later we’ll hear some expert perspective from Dr. David Steensma, associate professor of medicine at Harvard Medical School, and attending physician for the Adult Leukemia Program, at the Dana Farber Cancer Institute. Thank you all for joining us today. Let’s begin. Dr. Raza, I wanted to ask you just to start with the presentation of MDS and the common disease characteristics when you first meet somebody.

Azra Raza, MD: Thank you, James. It’s a very timely discussion, because myelodysplastic syndromes really are a disease of the elderly, and as our population is aging, we have more and more patients being diagnosed with myelodysplastic syndromes. And, the way they generally present, has to do with the consequences of cytopenia, which means that either they have an anemia and they’re getting tired or weak, or they start bruising because of low platelet counts, or occasionally they present with an infection.

For low-risk myelodysplastic syndromes, a number of patients are actually picked up serendipitously because they present for an annual physical exam to their primary care physician, and, there, a CBC would reveal that one of their blood counts is low, and this leads to further workup. So, typically, at presentation, they have weakness, fatigue, bruising, and occasionally, signs of infection.

James M. Foran, MD, FRCPC: I find that sometimes patients come in in a subacute way where they’re symptomatic with dyspnea or symptomatic of anemia, but it isn’t discovered. They go through a cardiac workup or something else for comorbid diseases. Do you think the comorbidities play into this, or the age or functional status of the patients when they come in to see you?

Azra Raza, MD: Definitely, because it is a disease of the elderly, so I think you bring up a good point that many of these patients, because of their comorbidities, get worked up for other things. Of course, once a CBC is done and one of the counts at least is found to be low, that always raises the level of suspicion about a primary bone marrow disorder.

James M. Foran, MD, FRCPC: Do you find many of your patients start on iron therapy before they see you, or that somebody tries to correct an anemia before it’s truly diagnosed?

Azra Raza, MD: Yes, for low-risk MDS where there is a pure anemia that they are presenting with. Of course, if there is more than one blood count that is reduced, then it’s rarer. But just for an isolated incidence of anemia, you are absolutely right. They will have taken iron, and folate, and sometimes B12, supportive care things like that. And then, eventually a bone marrow will be performed.

James M. Foran, MD, FRCPC: CBC is often an under-ordered test, I think, and often gets ordered later in the workup rather than earlier. I would advocate that people check it earlier when somebody comes in with a symptom as something I’ve noted. But, what are the drivers of disease progression in MDS?

Azra Raza, MD: Interestingly, myelodysplastic syndromes is a disease that is not always linearly progressive. It isn’t a steady decline in patient’s count. Very often, especially with lower risk MDS, which is two-thirds of patients, the progression of MDS is what I call punctuated equilibrium, which means some event happens and the counts have gone down at the molecular level. But then, the counts stabilize at their level for an indeterminate period until a second event happens, and then again they settle at that second level of low counts.

So, there is sort of a punctuation followed by equilibrium. This is more of a course in the lower risk myelodysplastic syndromes. For higher risk disease, more often than not, the progression is more aggressive or rapid, accelerated by, usually, the presence of multiple chromosomes being damaged or multiple mutations being present, etcetera.

James M. Foran, MD, FRCPC: I hope you don’t mind if I borrow your phrase of punctuated equilibrium. I think that’s a beautiful way to say that. And what about the risks of progression to AML? Is that an important thing, or is that something that you try to model at the beginning when you see a patient?

Azra Raza, MD: This is one of the really challenging issues in myelodysplastic syndromes. When a patient walks into my office, the first thing I’d like to know about that patient is, is their chance of survival high or low? And there is really no accurate way of doing it. With all the scoring systems, with all the classifications we have, we can still go completely wrong in our assessment of how rapidly a patient is going to progress.

I’ve looked at this very carefully, James, and what I’ve noticed is that 70% of the patients, whether they have low-risk disease or high-risk disease, will not progress to leukemia. So, even 70% of very high-risk MDS are not going to develop acute leukemia, but they’re going to die in a very short time. And they will die of MDS. So how do you die of MDS if you don’t develop acute myeloid leukemia? You die of MDS because of the increasing profundity of the blood counts. They fall so low that we cannot keep up with transfusions and supportive care measures anymore, and eventually they succumb to infection or bleeding.

James M. Foran, MD, FRCPC: Yeah, I think that’s an important point. Bleeding and thrombocytopenia are under recognized as contributors. And infections, and even the morbidity of transfusions, is under appreciated in how it either accelerates the disease or the decline.

Transcript Edited for Clarity