Doctors at Seattle Cancer Care Alliance (SCCA) and our founding organization Fred Hutchinson Cancer Research Center continue to search for new treatments and possible cures for myelodysplastic syndrome (MDS).
In addition to standard treatment options, we offer agents that are not commercially available but showed promise in pilot studies and are being tested in clinical studies. Examples include azacitidine (Vidaza) given by mouth (the commercially available drug is given by injection or infusion), clofarabine (Clofarex, Clolar) given by mouth, and a multikinase inhibitor (rigosertib [Estybon], used for people who have failed azacitidine and decitabine). We also have clinical studies testing different combinations of chemotherapy agents and other studies testing different transplant regimens, such as radiolabeled BC8 (anti-CD45), an experimental transplant conditioning agent.
A new chemotherapy drug called treosulfan has shown promise and may be useful for people with MDS who are having a transplant. Treosulfan is similar to an older chemotherapy drug, busulfan (Busulfex, Myleran), but it appears to be less toxic and may improve survival rates.
One research path has been to investigate how MDS develops—its pathophysiology, or what goes wrong in the bone marrow. By learning more about the chain of events that leads to severe cases of MDS, doctors hope to be able to block one or more of these events and at least stabilize the disease.
For instance, we studied azacitidine in combination with another drug, called etanercept (Enbrel). This combination resulted in improved blood cell counts in almost 70 percent of study participants. Responses occurred faster than with azacitidine alone, and in some people the bone marrow became normal. Several people treated this way were followed for three years and were still maintaining their improved blood counts and not needing transfusions.
Among the other drugs being studied for use in MDS are AMG-531, vorinostat (Zolinza), and others.
Researchers at the Hutchinson Center are using antibodies to deliver radiation specifically to disease-causing cells—in MDS, this means to cells in the bone marrow. This targeted radiotherapy lets doctors get more powerful doses of radiation where it’s needed to destroy the disease, while sparing most healthy tissue.
People who receive this treatment may be able to have a low-dose conditioning regimen before a bone marrow transplant. Low-dose conditioning tends to cause milder side effects. This combination of therapies was first used successfully in high-risk MDS patients here who had no other curative options.
Additional studies are trying to determine whether immune cells in a person with MDS can be modified so the immune cells will attack the MDS cells and eliminate them. This type of treatment is called immunotherapy.
More Research Questions
Researchers at the Hutchinson Center and SCCA are also working on a number of other topics related to MDS.
- If doctors can identify subtypes of MDS more precisely based on what they see in affected cells, they hope to come up with more specific treatments. They know that what we call MDS is actually a collection of several different diseases with some important distinctions. Ideally, doctors will be able to match each patient with the most effective drug, or combination of drugs, for his or her subtype and severity of MDS.
- Several studies are underway to figure out the best approach for patients with MDS who receive a bone marrow transplant. Researchers are investigating questions such as these:
- At which intensity does chemotherapy lead to better results with fewer side effects depending on a patient’s situation?
- At which risk level and which age should patients be considered for transplantation?
- What other factors about the patient or the disease can help doctors determine whether and when to offer a transplant?
- To help prevent MDS in the future or diagnose and treat it early, researchers are trying to understand what causes MDS, including:
- Whether changes in blood stem cells that occur naturally with age can provide clues about what goes wrong in MDS
- Whether factors in the environment play a role in MDS