Ryan Haumschild, PharmD, MS, MBA: I’d like us to transition to talking about prognostic models. Dr Zeidan, I’m going to turn to you for your expertise as we talk about the prognostic models used in myelodysplastic syndrome [MDS], or myelodysplastic neoplasms, as you mentioned earlier. Which do you prefer? What do you do for a low-risk patient vs a high-risk patient? What does that mean for MDS? Please explain that for our viewing audience.

Amer Zeidan, MBBS, MHS: This is a very important point. As I mentioned earlier, prognosis can vary significantly between patients. It’s very important to differentiate whether the patient is at significant risk of dying or progression to acute myeloid leukemia, because that will significantly affect which treatment options you’d recommend.

When we initially meet the patient, we usually try to give them what we call the risk score. There are multiple tools that we have traditionally used. Many were developed over the years, but the most commonly used ones include the International Prognostic Scoring System [IPSS]. This was first described in 1977 and then revised in 2012. Both systems use a blood count and look at how low the blood counts are. They use cytogenetic or karyotypic abnormalities and the blast count, how many blasts or cancer cells are present in the blood and bone marrow.

Using these parameters, you assign the patient a risk score that will put them in a prognostic category. Ultimately, those could give you 4 or 5 categories, but from a pragmatic point of view, you classify the patients in 1 of 2 big groups. One is called lower-risk MDS, and the other is higher-risk MDS. That’s important, because what you’d recommend for management is very different. For patients with lower-risk MDS, your focus is generally on the quality of life, because we haven’t had any treatment that has been shown to improve survival on those patients in a conclusive way. Our goal is to minimize their transfusion burden, improve their quality of life, and minimize their hospitalizations and complications of bone marrow failures, such as infection and bleeding.

Patients who have higher-risk MDS are at a significant risk of reduced life span. Their median [survival] could be 1 to 2 years without any treatment. It’s very important to try to alter the natural history of disease of those patients, and the way to do that is with hypomethylating agents and bone marrow transplants. Bone marrow transplant is the only potential way to cure patients with MDS. However, linking to what we mentioned earlier, it’s a disease of older patients. Most patients generally aren’t able to undergo bone marrow transplant, so most patients will end up with therapies that either improve quality of life or prolong survival, but you can’t cure MDS in the vast majority of patients.

Most recently, we’ve also used molecular alterations to affect the prognostic picture of the patient. The molecular IPSS was described this year, in 2022. This is another prognostic scoring tool that will add the molecular alterations that we see in more than 90% to 95% of patients with MDS so that you can refine your risk categorization. Still, I don’t think these scores should be taken as an absolute way of dictating treatment. You have to account for the patient goals, which clearly aren’t captured by any treatment or prognostic tool. You also have to account for comorbidities and coexisting medical problems, which also aren’t accounted for in these tools. You have to sit with the patient and go over all this to come up with a good treatment plan.

Ryan Haumschild, PharmD, MS, MBA: You did a great job describing it. I appreciate your detail from how you stratify patients to high-risk genetic molecular risk scores that you’re looking for. What also stood out to me is that this is a disease of aging populations, and it’s really tough. Not every center in the country offers bone marrow transplant, and not everyone treats patients who are as unique as MDS, so access to care is a barrier. Then we add on that a lot of these patients are older. Comorbidities, which you did a great job of highlighting, are extremely relevant in this patient population. As a provider, you’re trying to balance all these risks together to select the right therapy, which makes it unique. That’s why there’s so much education and an unmet need here.

Transcript edited for clarity.