Treatment Options in Myelodysplastic Syndromes - Episode 1

Heterogeneity and Presentation of MDS


Amy DeZern, MD, MHS: Hello, and welcome to this OncLive® Insights®, “Treatment Options in Myelodysplastic Syndromes.” I am Amy DeZern from Johns Hopkins University School of Medicine in Baltimore, Maryland. Joining me is Rami Komrokji from H. Lee Moffitt Cancer Center & Research Institute in Tampa, Florida. Today we’re going to discuss several interesting topics in the management of myelodysplastic syndrome [MDS], including new therapies. Let’s get started. Rami, could you begin, please, by describing the heterogeneity of myelodysplastic syndrome for us?

Rami Komrokji, MD: Absolutely. As you know, MDS is a collective term of bone marrow failure. Clinically, they are characterized by cytopenia, a tendency to progress to acute myeloid leukemia, but we definitely see a variety of disease and heterogeneity from biology, molecular mutations, and somatic mutations of cytogenetic abnormalities to the clinical presentation. Obviously, we can think of higher risk and lower risk MDS being almost completely separate behavior, but even among the lower risk, we know that there is a lot of heterogeneity. We have, for example, the 5q patients; they reemphasize on patients with MDS ring sideroblasts, so the SF3B1 mutation. There is a lot of heterogeneity even among those groups of patients and the behavior. We see patients who remain asymptomatic for a long time, and we see patients who are very heavily transfusion dependent. As we move forward, we have to think of the heterogeneity because for a long time, we did the clinical trials, including all those patients. We lumped patients as lower risk; some we treated. The reality is that’s not going to be the best way moving forward. I’m sure that all the clinicians have observed this and seen this heterogeneity and the difference in the behavior. Also, there is some host-related factors that they say is the course of the disease or how symptomatic is the disease is, but that’s something always to keep in mind: how heterogeneous is MDS. One day we’re going to be looking at those as separate diseases.

Amy DeZern, MD, MHS: Hopefully so.

Rami Komrokji, MD: Yes. You probably also could comment on your experience on how you see the presentation and the heterogeneity in the presentation. How do you get patients diagnosed with MDS? How do they get to you?

Amy DeZern, MD, MHS: I do think heterogeneity remains the consistent feature, right? Nothing is as stable as that 1 thing. Patients come in lots of different ways, and I do think it happens to matter whether or not they have lower- or higher-risk disease at the time of presentation. Some symptoms that can be seen across all categories of myelodysplastic syndrome can be fatigue, certainly cytopenias. Hopefully we meet them prior to transfusion dependence, though I will say many people come to presentation when they come to the emergency department with an extremely low hemoglobin or a bleeding event in the context of thrombocytopenia. Shortness of breath as the hemoglobin comes down may be the first thing that somebody complains to their internist about or a decreased exercise tolerance, something that prompts a physician, probably not an oncologist or hematologist, to check somebody’s complete blood count and recognize that 1, 2, or even 3 of the cell lines are down, perhaps a macrocytosis, and this prompts a series of events that brings them to your attention or my attention with a bone marrow evaluation that ultimately makes the diagnosis of MDS.

Some other common signs can be easy bruising. I feel like a lot of people do note this when we ask their review of symptoms, though it often comes up even in patients who are not truly thrombocytopenic, and the patients can have petechiae when they have platelets less than 10,000 or 20,000 per mm3. Then there are other people who spend a lot of time focusing on an internal fatigue that is distinct from the degree of anemia, distinct from any other treatments, and they just can’t explain why they don’t have any more of that oomph that they used to have, the get up and go. It’s really a challenge.

Transcript Edited for Clarity