A panel of medical experts discuss supportive care needs for patients with myelodysplastic syndrome.
Ryan Haumschild, PharmD, MS, MBA: Let’s pivot really quickly here and address some of the major morbidities of myelodysplastic syndrome that require treatment. Dr Mahmoudjafari, I’ll turn to you for this question. When we look at some of the major morbidities of MDS, what does a typical support of care for patients with myelodysplastic syndrome consist of? When should patients be considered for treatment beyond just support of care?
Zahra Mahmoudjafari, PharmD, BCOP, DPLA: Absolutely. I would change to probably the second question first. I think all patients are going to be treated with supportive care if it’s impacting their quality of life. We have blood transfusions to treat the anemia, thrombocytopenia. We have the oxygen and variable growth factors that help the cells mature, such as epoetin, filgrastim, or potentially even products like Promacta [eltrombopag], platelet growth factor. We have antibiotics to treat infections, which honestly the common adverse effect are low white blood cell counts. We have lots of different supportive care options. I would say for those patients that we decide to treat beyond supportive care, in addition to supportive care, would be those high-risk patients or the patients where supportive care is no longer an effective treatment option. Again, in line with its own treatment goals and how aggressive we want to be. We are trying to hit a certain goal, such as getting a patient through a transplant, which is again the only curative therapy, then we’ll be more aggressive and use other agents. There’s a lot of push and pull involved.
Ryan Haumschild, PharmD, MS, MBA: Excellent. Well, I want to talk about myelodysplastic syndrome as it’s related to anemia because we know that’s a big deal within the disease state. We know that’s something that we try to address as practitioners. Dr Mancini, how is myelodysplastic syndrome–related anemia treated? What are some of the strategies that are successful? What are some of the key ones that you see most used across the landscape?
Robert Mancini, PharmD, BCOP, FHOPA: For the most part, if you’re focused on the MDS-related anemia and focused on how to treat that, most of the time we’re going to be discussing the lower risk patients, where the goal of therapy is to decrease transfusion needs, reduce risk of progression to AM [acute myeloid leukemia], and improve survival. Our ultimate goal with any type of therapy is to reduce the need for blood transfusion, as we know that chronic blood transfusions increase the risk of iron overload, thrombotic events, infection risks, and have been associated with decreased survival. A lot of that’s related to the effects of the previously mentioned toxicities, as well as increased need for transfusion impacts on quality of life, as we already talked about.
In patients with symptomatic anemia as a primary focus, you would first stratify based on whether they are deletion 5q. If so, you would go primarily towards lenalidomide. Otherwise, you would look at presence of ring sideroblasts and serum EPO or epoetin levels to determine the course of action. If you refer to the NCCN [National Comprehensive Cancer Network] guidelines, there’s a nice algorithm that can be followed, but we often find there are patient-specific factors that lead to deviations from some of those protocols. If you have a patient with low levels of ring sideroblasts and a serum EPO less than 500 micro µ per million, you would start with erythropoietin-stimulating agents, or ESAs, such as epoetin or darbepoetin. If their EPO is greater than 500 micro µ per million, it would be suggested that they likely not respond to ESA therapy and therefore may have to rely on more aggressive therapies usually reserved for more high-risk patients, such as immunosuppressive therapy or hypomethylating agents, such as azacitidine, decitabine or the oral agent, which is a combination of decitabine and cedazuridine. Decitabine as your treatment and cedazuridine.
It’s an enzyme inhibitor that helps improve that oral viability of the hypomethylating agent. Next, if we looked at patients with greater than 15% ring sideroblasts or greater than 5% with that SF3B1 gene that Dr Mahmoudjafari talked about, that gene is associated with ring sideroblasts, so even if they don’t meet that 15% threshold, 5% with that specific genetic malformation, you could go towards the human activin receptor inhibitors that inhibits transformation, transforming growth factor b, which is a medication called luspatercept. This product is meant to block TGF-b, allowing for better differentiation and proliferation of those erythro-growth factors, thus improving the anemia.
If a patient has anemia with either thrombocytopenia or neutropenia, so in other words multilineage dysplasia, then you would likely be starting out with more aggressive therapy for those higher risk patients. The other thing that I think is important in factoring how we treat the anemias is, like I said, our goal to reduce transfusion burden and therefore risk of iron overload. Iron chelation is important, regardless of the degree of red blood cell transfusion dependencies patients are facing. Iron chelation therapy has been shown to improve survival in lower-risk [patients with MDS], regardless of their transfusion dependency, by almost doubling that survival time we see in this patient population, especially the longer they are on the iron chelation therapy. There are 3 products on the market; however, only 2 are currently recommended in MDS and those are deferasirox and deferoxamine. That former one, the deferoxamine, is being contraindicated in high-risk patients because we’ve seen an increase risk of GI [gastrointestinal] bleeds and renal hepatic impairment. These patients probably are not going to benefit from long-term chelation therapy because of the high-risk nature of their disease anyway. So, if you look at the NCCN guidelines again, deferasirox is recommended for low risk while deferoxamine is recommended for any [patient with MDS] who could require iron chelation therapy. That’s typically what we see here. We get them started on that. Again, ring sideroblasts. It’s that deposition of iron in the mitochondria. It exists whether or not these patients are getting those therapies up front already.
Ryan Haumschild, PharmD, MS, MBA: That was a great overview because it goes into the fact that anemia is not anemia within myelodysplastic syndrome. If a patient’s low, intermediate, or high risk, how do we follow the NCCN guidelines? Unique considerations like the presence of ring sideroblasts impact what treatment would be best there. What therapy should a patient be trying in the frontline setting? Obviously, iron chelating agents pretty much reduce the burden on the patient and improve outcome. Great, great overview there. I think there’s a lot of options out there and you can tell that it requires a little bit of advanced knowledge to make sure that we’re setting the patients up for success and we’re sequencing agents appropriately based on their unique factors.
Transcript edited for clarity.