Defining and Assessing Risk in Patients with Myelodysplastic Syndrome
Dr Savona and Dr. Zeidan define lower- vs higher-risk MDS, describe their approach to risk stratification, and share how assessing risk is critical for developing treatment plans for patients.
EP: 1.Understanding Myelodysplastic Syndrome: Molecular Mechanisms and Diagnosis
EP: 2.Defining and Assessing Risk in Patients with Myelodysplastic Syndrome
EP: 3.First-Line and Second-Line Treatment Options for Lower-Risk MDS
EP: 4.Imetelstat in Lower-Risk MDS: IMerge Trial Overview and Efficacy Outcomes
EP: 5.1-Year Follow-up of Efficacy Data and Safety Outcomes of Imetelstat in Lower-Risk MDS
EP: 6.Disease Modifiying Therapy in Lower-Risk MDS
EP: 7.Insights on Imetelstat in Lower-Risk MDS: Safety Outcomes
EP: 8.Clinical Implications and Positioning of Imetelstat in Lower-Risk MDS
Dr. Amer Zeidan: So Mike, risk certification is super important in MDS. And this is something that I think is always important to emphasize to our colleagues in the community. Can you talk about your approach to risk stratification?
Dr. Michael Savona: Sure. Dr. Zeidan was quite eloquent in talking about the ways by which we might be able to diagnose people and stratify people without even looking in their bone marrow. Of course, we can't do that yet, but that's kind of the direction we're going. And that gets to the point of risk stratification, looking as I like to tell patients, from 50 foot up with a drone and then 50,000 feet up with a spy plane, and then from a satellite from space. So in that analogy, what we're looking at from far away are big changes that we can see morphologically on the bone marrow and clinical changes like anemia and thrombocytopenia and neutropenia and morphologic changes that are obvious to the eye. And then when we get kind of zoom in a little, some big structure abnormalities that we can see in the DNA with chromosomal changes that are typical such as monosomy 7 or deletion 5Q or, deletion 13 or minus Y in MDS or like the drone in this analogy, getting down really close and seeing specific, even single nucleotide missense mutations which can actually have considerable impact over time on generation of a more high risk disease. Now, risk stratification uses these clinical pieces and the morphologic pieces, how bad is the anemia? How bad is the neutropenia? And morphologic changes, you know, are there blasts in the marrow, this kind of this leukemic type picture in the bone marrow with anywhere from five to 10 or 10 to 20% of cells being blast. But as we've gotten a little bit smarter in our, and we've gotten to look at larger data sets, it's become clear that we can rely more on these mutations. And both Amer and I have been involved in this through the years. And I would encourage you to look at www. mds-risk-model.com where you can see in the new IPSS Molecular IPSS-M risk calculator. Our first international prognostic scoring system was devised in the 90's looking at clinical features. This was refined with the IPSS-R or the revised a decade later where we got a little bit more discrimination between the higher and low risk patients. And now with IPSS-M, we can look at how some of these specific mutations, can really give us a fairly accurate idea of what the risk of developing acute leukemia really is. And these risk categories from very low risk to very high risk, have median survivals that vary from less than a year to all the way into decade or more for the very low risk. So it's really important to get a sense of, what we're talking about before we start treating the patient because if a patient's diagnosed at age 80 and they have a median survival of eight to 10 years with their disease, then maybe they can be treated a little bit more symptom focused if a patient is, or even observed. If a patient is high risk and their chance of getting leukemia is in the 80 to 90% range, and then their 60's or 70's, well, this is going to end their life if we don't do something more aggressive. So that risk stratification is very important. I see a lot of high risk patients at a referral center or patients with low risk who have been low risk for a while, but refractory to multiple therapies. But overall in the community, the grand majority of patients with MDS are diagnosed lower risk. Some of those patients never progressed to high risk. But as you'll see later on this discussion, quite a few of them get pretty sick with low risk disease and it could be a fairly morbid disease, even if the survival is pretty long.
