Mikkael A. Sekeres, MD: We’ve been talking a lot about the biology of the disease, risk stratification, and genetics. We tend to talk a lot about that with MDS [myelodysplastic syndrome] because, frankly, we don’t have a lot of treatment options, so we spend a lot of time talking about the biology. Once someone has a diagnosis of higher-risk MDS, what are the clinical implications? How do you start to think about treatment?

Yazan Madanat, MD: That’s a great point. And to comment on the risk score that you mentioned that’s coming out, this would be fantastic for better personalizing therapy and recommendations for those patients. We get those NGS [next-generation sequencing] panels and molecular testing for all those patients. It’s become a standard of care, but we don’t fully know how to incorporate them, other than we know that certain mutations have higher risk. But which patients should go on to transplant and which patients may be OK just monitoring and watching those counts at the time they would maybe have an AML [acute myeloid leukemia] progression?

This is where those clinical implications come into play. From a treatment perspective, when I see patients with higher-risk disease, the first question I ask myself is, are they going to go on to get an allogeneic transplant, and are we going for a curative therapy? At the 2020 ASH [American Society of Hematology Annual Meeting], they presented nice data that were also presented at the TCT [Transplantation & Cellular Therapy] Meetings for patients up 75 years of age who proceeded with an allogeneic transplant. That showed a pretty clear survival advantage for those patients. As you know, getting to transplant may take a few months. That process is undergoing, but getting the disease burden under better control would be the most common approach to therapy rather than watching the patients, even if their blasts were acceptable for transplant, to prevent that AML progression and maybe reduce the disease burden, though some argue against that.

My general approach would be to start with hypomethylating agent therapy. Nowadays, we have 2 older ones: the azacitidine and IV [intravenous] decitabine and then oral decitabine, or decitabine-cedazuridine, which has been approved in the past year as an oral option for patients with higher-risk MDS. Hypomethylating therapy is the standard of care in this day and age. Getting an allogeneic transplant or having that patient meet with a transplant physician getting the HLA [human leukocyte antigen] typing in process up front would be my way to go, and then reassessing the disease at 4 to 6 months, depending on the transplant plans.

If they don’t have any plans to go to transplant, I’d delay it up to 6 months, because most patients would have some form of response by then if they’re going to respond. If the transplant things are ready, we may push the marrow a month or 2 earlier. That’s to decrease AML transformation and to prolong survival. As you’re aware, the trial that really showed the survival advantage was with azacitidine—the AZA-001 trial—and that would be the preferred option for me as a starting therapy.

Transcript Edited for Clarity