Possible Treatment Options for Myelodysplastic Syndromes

Hetty Carraway, MD: I just want to acknowledge a lot of work that you’ve done in your career for patients with myelodysplastic syndrome [MDS] and ask you some questions about the lower doses that you’ve been investigating for patients with myelodysplastic syndrome. What has your experience been like? What might you share with the audience today about what your institution has done with regard to newer therapies for patients, whether it’s the lower-risk hypomethylating agent approach or novel therapies that we need to look for in the upcoming year or years?

Guillermo Garcia-Manero, MD: Thank you, Hetty. You’re too kind, because you’re part of this effort as much as I am. First, the message for the audience is that patients and their families need to be engaged. We talked earlier about how you need to be active with this disease. These are very complex disorders. Not to be critical, but many times, even hematologists may not be 100% on top of what’s happening or the latest. Medicine is getting very complex. Hetty and I treat two or three disorders. Beyond that, we probably don’t know much. So it’s really critical for the families and the patients to be engaged.

In my opinion, it’s really critical for families to ask these questions that we talked about earlier: “What is my risk? What are my chromosomes? What are my mutations?” You really need to ask the doctors and be aggressive in a positive way in terms of the therapy working, what is next, and if there’s a clinical trial close by that could help you. This is a big country, but we have big research centers all over that likely will have some degree of expertise or a clinical trial.

With regard to your specific question, we’re going through a transformation in our ability to treat patients with this disease. Maybe we can talk about high-risk disease someday. There are a lot of new doublets that are very effective. In low-risk disease, we’re seeing something that is eventually going to be very positive. You and I, through the MDS Clinical Research Consortium in the United States, work in these lower-risk trials and try to use the hypomethylating agents at a lower dose. That was an intuitive concept because we thought that lower doses could be effective and possibly less toxic. It turned out that, for some subset of patients with lower-risk disease, they can actually be beneficial.

We are also developing oral hypomethylating agents. Hypomethylating agents are given subcutaneously or through IV [intravenous] for three, five, or seven days a month. This gets tiring. The injections are short, but they take some time, and that may be a week of your month that goes away. So for many years, we’ve been working on oral hypomethylating agents. We now have two of these compounds that I think are going to help our patients very much, because they are oral and because they’re going to allow us to actually take a lower-intensity approach without coming in so many days during the month for the therapy. There is a revolution on treatments, and these treatments may be easier to receive and more patient-friendly. This is going to be a major breakthrough for our patients.

We believe that a lot of these are some type of combination where it’s not just one drug or the other. You may see combinations of all these compounds helping our patients and hopefully, at some point, transforming and improving their survival. Thank you for that, Hetty.

Hetty Carraway, MD: Exciting things are to come in the upcoming years with regard to what therapies we might use in the up-front setting in ways that are different from the current state of affairs. Combination therapies are likely to emerge for patients with MDS, inclusive of some of the targets for the mutations on the blasts or the cancer cells themselves. They then allow for combinations with the backbones of therapy that we use. We have specific agents that are going to be targeting TP53. Many of us in this space of MDS and AML [acute myeloid leukemia] are very excited about some of these TP53 modulators that may be used in combination with hypomethylating-based therapy. Those studies are soon to emerge as well.

There are exciting things that are ongoing in the clinical trial space. There’s a lot of hope for the future for our patients with MDS, even with higher-risk MDS. It’s important, exciting, and at the forefront of research.

Transcript Edited for Clarity