Current and Future Treatments for the Management of Myelodysplastic Syndrome - Episode 16
Experts share their experience with oral hypomethylating agents in myelodysplastic syndrome and consider how else these agents might be used moving forward.
Bart Scott, MD, MS: Access to care is a big challenge, particularly for patients with MDS [myelodysplastic syndrome]. The median age of diagnosis is 72. Many of these patients face challenges with transportation. I work at the Fred Hutchison Cancer Research Center, located in Seattle. We serve as a regional academic center for a large catchment area including Alaska, Wyoming, Montana, Idaho, and Washington. We also get patients as far away as Hawaii, and the remote reaches of the Aleutian Islands of Alaska, so it can be challenging for patients to come and receive the treatments at any center, not even an academic center.
Many of these patients don’t have access to IV [intravenous] infusions, so the approval of oral hypomethylating therapy would be of great benefit to them because then they don’t have to come into a place to receive their treatments; they can receive their treatments locally. Their blood counts would still need to be monitored, but they can go to their local laboratory for that, and they can be monitored for other types of symptoms remotely through telehealth visits, for instance.
There’s a big challenge for patients, particularly with MDS, because as patients get older, it’s common that they don’t drive as much, and they don’t want to face traffic, particularly in Seattle. It would be helpful to have a way to get patients treatment that didn’t require them to go to a location to receive that treatment.
In regard to wait times to receive hypomethylating therapy, I can only comment on our own personal experience. Pre COVID-19 [coronavirus disease 2019], we did have an issue with clinic availability. It was difficult to get patients scheduled for IV infusion times. Now our infusion center has a lot of space available, but that’s not expected to always be the case, so it can sometimes be difficult to get patients scheduled for their IV infusions. When patients come for the IV infusions, there is about a 20-minute wait, and then the IV infusion itself takes about 1 hour.
Amer Zeidan, MBBS, MHS: There are several challenges. One of them was the lack of effective therapies, and we are finally having what I refer to as a therapeutic revolution in MDS with many good agents being tested, and they are in advanced parts of clinical trials. We could be in a situation similar to what happened with AML [acute myeloid leukemia] where you have a long period with no approved therapies, and then you have 8 drugs approved within 2 and a half years. We finally had our first approval with luspatercept after 14 years of no new therapies. This drug, the oral decitabine, is in front of the FDA for consideration of approval. Other agents are in advanced clinical trials.
All of this is very good for the patients. It might provide more options, and as we get more active therapy, we are going to be able to treat more patients. In our real-life and effectiveness analysis, what we have found at the population level is that many patients with MDS are not being treated, and part of that is related to the lack of effective therapies and potentially the lack of oral options for high-risk MDS. Having oral options and having novel therapies is going to have a major impact for many patients with MDS.
One of the bigger challenges in MDS compared to acute myeloid leukemia is that the number of actionable mutations that you can target is somewhat lower in MDS. In AML, around 40% to 50% of patients will have an IDH [isocitrate dehydrogenase] or a FLT3 mutation, which now have approved therapies, oral inhibitors. In MDS, those mutations are somewhat rare, they are less than 5% to 10% for the IDH and probably less than 5% for the FLT3 mutations, so they are not often present.
Individualizing therapy is based on precision medicine or genetic alterations outside of using deletion 5q for low-risk MDS. Lenalidomide is not as commonly used in MDS, but we are using other ways of individualizing therapy. For example, having ring sideroblasts for patients with lower-risk MDS, there could be a way to use luspatercept, especially after ESA [erythropoiesis-stimulating agents] failure. There is another way to think about other therapies that are being studied. For example, for the TP53 mutation, there are now agents in clinical trials that are going after the TP53 mutation, which we see in 15% to 20% of AML and MDS patients. We're going to move more in the direction of individualized therapy, but MDS is still lagging behind AML in that regard.