In patients with myelodysplastic syndromes (MDS), a cancer in which the bone marrow does not make enough healthy blood cells, red blood cells may not mature and function properly. As a result, about 85 percent of patients with MDS develop serious anemia. Since roughly half of patients do not respond to current therapies aimed at increasing red blood cell production, many end up relying on frequent transfusions to treat the symptoms associated with anemia.
Sandra Kurtin, Ph.D., ANP-C, AOCN, University of Arizona Cancer Center, believes MDS will be in the spotlight at this year’s American Society of Hematology (ASH) annual meeting. In a Q&A, Kurtin discusses current research to uncover why red blood cells don’t mature properly in MDS and how targeting different stages of their maturation may lead to much-needed new therapeutic options.
What advances in the research of MDS will hematologists learn about at this year’s ASH meeting?
“The International Working Group for the Prognosis of MDS will be meeting to look at the molecular underpinnings of MDS and to identify groups of patients by risk. We’ll be looking at some molecular targets for potential new therapies in MDS.
During the meeting, I look forward to seeing data about some of the novel pathways implicated in the development of blood cancer in certain groups of patients. Researchers now believe that certain mutations within these pathways may help predict survival chances for some patients with MDS.”
Why has developing effective therapies for MDS been challenging?
“MDS is complicated. It’s been difficult to pinpoint a single pathway that overcomes the abnormalities inherent in MDS. For instance, the tumor cells’ surroundings, known as the microenvironment, may play a role. Current therapies target cancerous cells, but may not be targeting the microenvironment. Additionally, molecular abnormalities and abnormalities in the spliceosome are known to contribute to the pathobiology of MDS. Today, the only potential cure is a stem cell transplant, but many patients may not be eligible for one.”
Why is a stem cell transplant not an option for most patients?
“While some patients may not warrant immediate treatment, the only way to overcome the abnormalities of MDS is to replace the genetic profile through an allogeneic bone marrow transplant. But that is associated with several risks. Transplantation is typically considered for patients with higher-risk MDS.
Usually, patients have to be younger than a certain age and otherwise healthy. Some centers are now allowing transplants up to the age of 75. The median age of diagnosis for MDS patients is 76.”
What other treatment strategies are being explored for MDS?
“Treatment for lower-risk MDS is aimed at improving cytopenias, including anemia and reducing the need for transfusions. Meanwhile, the primary treatment goal for higher-risk MDS is to extend survival.
Doctors use treatments such as erythropoietin to stimulate the red blood cell production in some patients with lower-risk MDS. An unmet medical need remains in patients that do not respond or do not maintain response to supportive treatment.”
Now we’re coming to realize that transcription factors and other molecular attributes also regulate the production of these cells.
How are researchers working to understand the biological mechanisms that lead to MDS?
“Pathologists are still exploring the ‘normal’ process by which blood stem cells commit and differentiate to form all the different types of blood cells within the bone marrow. We used to think that the process was primarily driven by growth factors. Now we’re coming to realize that transcription factors and other molecular attributes also regulate the production of these cells.”
What are the most important unanswered questions in MDS research?
“We’re trying to understand why MDS is such a heterogeneous disease. Why do some patients have a slow-growing disease while others have a more aggressive malignancy? What are the mutations that make it different? We’re trying to identify targets for drugs within those mutations.
Among the therapies highlighted at ASH will be those aimed at novel targets. Some new therapies are combination regimens using different classes of drugs, and some are novel single-agent therapies that may be combined with other treatments in the future. Therapies approved for acute myeloid leukemia, which evolves from MDS, are also being explored for MDS. There’s finally a lot of exciting research after all these years.”
To learn more about these rare cancers are negatively impact the daily lives of patients, read “New Survey Reveals Myelodysplastic Syndromes Leave Patients Feeling Fatigued.”