Evaluating MDS Treatment Pathways

Drs Mahmoudjafari and Mancini evaluate MDS treatment pathways and offer potential needs for switching treatment strategies.

Ryan Haumschild, PharmD, MS, MBA: We need to evaluate how this treatment’s working. Because we know at a lot of centers, if someone’s transfusion-dependent, we have to know are they transfusion-dependent? How often are they getting transfusions? Is it happening at an outside facility? Is it something that we have to keep track of? Is it happening in-house? How do we monitor that patient so we establish clear shared decision making around those goals? Dr Mahmoudjafari, I’m going to come to you on this one. In your experience, how do you evaluate the treatment? How long does treatment with ESAs work before any type of resistance is developed?

Zahra Mahmoudjafari, PharmD, BCOP, DPLA: I totally will respond with this. Typically, with all these patients in clinic, they’re coming to see us very frequently. Thus, we’re able to monitor trends and get a sense whether or not the patient is improving. It’s important to stress patience in this disease state, and it depends on how aggressive we want to be. Sometimes it’s evident that it’s working. Indications report improvement in their fatigue levels as well as their overall quality of life. Other times it’s not as clear until we formally assess for genetic mutations. With regard to ESA specifically, we know that it takes about 6 to 8 weeks to assess response to the ESAs so it’s difficult to predict exactly how long the ESAs work before resistance is developed. Most responses to ESAs occur within 3 months of treatment and have a median duration of about 15 to18 months. In eligible patients, who have lost response to a single agent ESA, there has been1particular study that found the addition of GCSF, 1 to 2 units per kilo, subcutaneously can rescue that response in up to 20% of cases. Sometimes we’ll do dual therapy, but the good thing is that we typically see this by following our hematologic parameters and making the necessary intervention. Long story short, being patient is easier.

Ryan Haumschild, PharmD, MS, MBA: One of the biggest takeaways I had is ESAs may be part of a patient’s journey, but we must constantly be evaluating because a patient may not be responding and it’s really important to make sure that we’re not just having that patient be on chronic ESA if they’re not responding and that we’re intervening early enough. Sometimes within the myelodysplastic syndrome environment, I think that’s one of the concerns. How often are we changing therapies when appropriate? Are we monitoring them closely enough so that we don’t have a therapy that is causing to still be transfusion dependent, and they’ve gone through that trial period? We got to make sure we get a response. So, thanks for walking us through that. Thanks for highlighting some of those key differences and really when to switch therapies or when to dose escalate. I think those are important things that we need to be aware of as practitioners.

When we talk about the different type of treatments and switching therapies, Dr Mancini, I’m going to look to you for this one because I feel like this is something that might be part of a journey of a patient with myelodysplastic syndrome. When you’re switching, what are the factors that you evaluate and how do you monitor for when to consider an alternative therapy like we just spoke about? Lastly, as we develop these treatments, it’s really important to know that some of them have titration associated with them. How do we know when to titrate? How do we know when to evaluate hemoglobin levels? Also, how do we know to pay attention to that transfusion dependency that patients may have even if it’s outside of our organization? It might be tough to track down those transfusion occurrences. Talk us through that a little bit and how assist practitioners can be aware of those factors when we’re dosing a patient.

Robert Mancini, PharmD, BCOP, FHOPA: I don’t know how much I can add to what Dr Mahmoudjafari just said. Those are our key factors. When we look at determining whether or not therapy is working, that’s what helps us determine whether we’re going to switch therapy. So again, I think the biggest guide to switching therapy is symptomology and then the corresponding labs. For most of these patients, you’re looking in response to their hemoglobin or other labs if they have thrombocytopenia and neutropenia as well. If they’re fatigue is not improving and they aren’t improving their counts, and more importantly, we don’t get them to be transfusion free, then that’s when we need to look at alternative treatments.

Someone starting with an ESA would potentially switch over to Luspatercept or more aggressive therapies. In some situations, if they have any initial response and they lose that response, then you need to consider disease progression as well. We talk about just not responding to therapy, but also we need to consider if their disease is progressing. There is a chance that these can progress, potentially transform. So, if you have a patient who is responding and then all of a sudden loses that response, then we need to reevaluate. We need to get a new bone marrow biopsy, update diagnosis, or plan of care. The other thing you mentioned Dr Haumschild, was the titration. I would love to say it’s hard, but it’s not, it’s well laid out in the package inserts for all the products that we use. It explains when we titrate and by what degree. We leverage that in our treatment plans within our EHR that it’s laid out there. We know how to make those adjustments. You have those dose buttons. Lots of ways to make that easy to utilize. Though I would say, we titrate per the package inserts. Sometimes we may be a little more aggressive than that stepwise approach, depending on if there was no response at that first level, we may jump up more than1level at a time. I think it’s laid out there and you must play in terms of your individual patients.

Ryan Haumschild, PharmD, MS, MBA: The dose titration is so important. I feel like that’s where pharmacists come into play because, using your example of an agent you mentioned, Luspatercept. So, patients finish their course of ESA transition to Luspatercept. The pharmacist a lot of times is the one that’s going to be there monitoring if there are any type of dose modifications or escalations that are needed. Based on how the patient’s responding, are they transfusion dependent? Do we stop? Did they lose some of that transfusion dependency? Do we need to dose escalate and how do we work with our provider teams to make sure we’re doing that in appropriate time? We don’t want a patient sitting on a dose if they’re not getting that therapeutic effect, especially if there’s options to dose titrate over time and monitor. Like you said, we need to make sure that patients when they’re progressing too, that we get them off therapy and we switch to something else.

One other thing that I think was so key to what you were talking about was the utilization of order sets. We have so many practitioners across many of our integrated delivery networks, some are very specialized like with the myelodysplastic syndrome. They’ll probably have this at the front of their minds, but we also know that there’s a lot of general hematologists, especially in the community that are trying to do a great job for their patients. There’s unique nuances to these therapies, sometimes to create standardization across many of the different practices. This is to build that into the EMR. How do you create an order set with the dose escalations as well as the modifications that are readily available? How do you differentiate for some medications indication of b-thalassemia myelodysplastic syndrome because those dose escalations might be different? I think you hit on some of those key indicators, and I think that’s really where pharmacists come into play is to make sure that we’re interviewing the patient, we’re doing a reconciliation of outside transfusions, and internally looking at hemoglobin levels and creating a recommendation of the team. Then, building that order set that I think really provides that framework for success.

Transcript edited for clarity.

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