Combinations May Confer Benefit in MDS Management

Caroline Seymour
Published: Wednesday, Oct 10, 2018

There are also studies that are looking at combinations of the IDH inhibitors as well as studies that are looking at checkpoint inhibitors. Those studies will be presented at the 2018 ASH Annual Meeting.

Where is research headed now?

A lot of clinical trials are focusing on patients with MDS who have already been exposed to a hypomethylating agent. For patients with lower-risk disease who have already received a hypomethylating agent, their median survival is less than 1.5 years. Technically, we would say that they have lower-risk disease, but in truth based on their survival, it's closer to a higher-risk disease. Patients who have higher-risk MDS who have already been exposed to a hypomethylating agent have a median survival of 4.5 to 6 months. The future of clinical trials is going to focus on this group of patients who have already been treated with a hypomethylating agent, and frankly are quite desperate for a better therapy.

What is the role of stem cell transplant in this paradigm?

For patients who have higher-risk disease, we discuss transplantation at diagnosis. Transplantation is the only cure for MDS. Though azacitidine may prolong overall survival, every therapy we have will ultimately fail our patients. We also will consider [transplant] in patients with lower-risk disease but who have high-risk molecular abnormalities, such as p53 or multiple molecular abnormalities.

What are some of the biggest challenges with MDS?

One of the biggest challenges with MDS is that it's a complicated disease. In chronic myeloid leukemia, the BCR-ABL translocation causes the leukemia, so it's reasonable to think that a drug could target that abnormality and make a significant impact on survival. In fact, that's what has happened with multiple tyrosine kinase inhibitors. With MDS, the typical patient at diagnosis may have 3, 4, or 5 molecular abnormalities, so to think that we can develop 1 drug that will target an abnormality is really full hearty.

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