An Introduction to MDS: Initial Diagnosis and Patient Risk Stratification

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EP: 1.An Introduction to MDS: Initial Diagnosis and Patient Risk Stratification

EP: 2.Clinical Insights on the Treatment of Patients with High-Risk MDS

EP: 3.Targeting CD47 in MDS: Reviewing the CD47 Pathway and Key Trial Data

EP: 4.The Future of Treatment for Patients with MDS

Dr. Naval Daver: Hello and welcome to this Cancer Network OnView Program titled, targeting CD47 in Higher Risk Myelodysplastic syndrome, MDS. My name is Naval Daver. I am an associate professor in the Department of Leukemia at the MD Anderson Cancer Center in Houston, Texas. Let's get started.

The general presentation of patients with MDS or myelodysplastic syndrome is usually with cytopenias. These include anemia or low hemoglobin; low platelet counts or thrombocytopenia and neutropenia. And most of the clinical manifestations that we see are due to these cytopenia. So because of the anemia, patients may have shortness of breath, fatigue, weakness, dyspnea, and exertion. Because of the low neutrophil count or ANC, they may be prone to infections. Many of the patients actually when they present, come with infections. These could be bloodstream infections, lung infections like pneumonia, bladder infections or others. And in some more severe cases of presentation of MDS, we may actually see significant thrombocytopenia or low platelet where the patients may have bruising or bleeding into their skin or from other organs. So these are usually the main manifestations. Now, usually along with this, what we see is when we do an evaluation that there are abnormal dysplastic cells in the marrow, which are called blasts or MDS cells, and it is because of these abnormal cells that the production of the normal hematopoietic cells has been shut down or decreased significantly.

The prognosis and disease cause in a new diagnosed patient with MDS is quite variable depending on the risk stratification or the prognostic assessment of that patient. So there have been many different prognostic scoring systems that have been used, the one that has been most commonly used in the last five years is what we call IPSSR, International Prognostic System Score Revised. But more and more now we are moving towards integration of molecular data in the last three to four years using a molecular IPSS or Integrated Prognostic Scoring System. But the bottom line is we look at a group of features. These include bone marrow blasts, the degree of cytopenias including anemia, thrombocytopenia, neutropenia, the transfusion requirement, and then more and more molecular factors mutations such as TP53, ASXL1, RUNX1, ECH2, and putting all of that together. There are actually now computerized online scoring tools that can be used very quickly within 30, 40 seconds. Once you put the information in, it will give you a personalized specific expected prognosis and response to treatment for your patient. This could vary from anywhere from 70% to 80% being alive at five years in the low and very low risk groups of IPSSR to median survivals of 12 to 14 months on the other extreme in the patients who are very high risks. So I think it's really important to use a personalized prognostic assessment because it could be extremely different in different patients with MDS, and this could also impact the selection of treatment, as well as potential need for allogeneic stem cell transplant.

The biomarker testing that we usually use is a combination of chromosome analysis called cytogenetic analysis as well as molecular analysis. More and more we have been getting larger molecular panels and data over the last five to seven years has shown that these have a very clear and important prognostic impact in addition to cytogenetics. When we look at cytogenetics, these are broadly divided into three groups. Favorable, intermediate, and adverse. Favorable include chromosomes such as 20Q5Q in certain cases, intermediate includes the big bulk of other cytogenetic abnormalities and unfavorable includes the ones that we are concerned about and will be considering ALLO transplant early on. This includes chromosome 17, chromosome 75 complex karyotype and others. Now on top of this we are overlaying the molecular information and certain molecular markers have a very high prognostic impact. These include TP53, which has a very significant negative prognostic impact, but also for treatment selection we are looking at molecular markers such as IDH1, IDH2, FLT3, because there may be different treatments targeting those. So, combination of chromosome analysis and molecular features usually helps us do a full biomarker assessment of the MDS.