Why has developing effective therapies for MDS been challenging?
MDS is complicated. It’s been difficult to pinpoint a single pathway or target that overcomes the abnormalities inherent in MDS. For instance, the tumor microenvironment, the cells in the bone marrow that provide growth factors and other cells essential to cellular growth, may play a role. Most current therapies target cancer cells but may not effectively target 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. Transplantation is typically considered for patients with higher-risk MDS. This is a very complicated treatment process that is associated with substantial risk. As a result, patients must have good organ function and be fit enough to undergo this treatment. Most centers have an age limit of 65-70, with a few centers allowing transplants up to the age of 75. The median age of diagnosis for MDS patients is 76, so the majority of patients with MDS do not meet this criterion.
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, though an unmet medical need remains in patients that do not respond or do not maintain a response to supportive treatment.