Quality Over Quantity: Expert Weighs in on Luspatercept for Myelodysplastic Syndromes

Kirollos Hanna, PharmD, BCPS, BCOP, FACCC, the director of pharmacy at Minnesota Oncology and assistant professor of pharmacy at the Mayo Clinic College of Medicine, recently joined Pharmacy Times in San Diego, California, at the 65th American Society of Hematology (ASH) Annual Meeting & Exposition, December 9-12, 2023, to discuss myelodysplastic syndromes (MDS). Hanna provides an overview of the disease— which is often associated with severe anemia and may progress into acute myeloid leukemia (AML). He also discusses current and new treatment options like luspatercept, whose real world efficacy aligns with clinical efficacy, according to a recent claims study.

PT Staff: What current treatment options are indicated for myelodysplastic syndromes?

Kirollos Hanna, PharmD, BCPS, BCOP, FACCC: So when we look at patients with MDS, there's really an armamentarium of therapeutic options available for these patients. However, majority of it has really been centric around a lot of the supportive cares.

One thing that we do know about MDS patients is that we're not going to cure this disease [and] these patients live a very long time. [But] throughout the course of their treatment journey, they do become refractory to many of the supportive care measures that we have. For example, if you look at patients, even with low risk, in the US, the likelihood of them going to have high risk MDS may be something of more blast involvement, maybe even transforming into an acute myeloid leukemia (AML). There's quite a large prevalence where this disease does mutate and differentiate itself throughout the treatment course. So, 1 big challenge that we do see with the MDS patient population is anemia, right? And majority of these patients will present with anemia, and a good chunk of them will start to require transfusion dependency.

Available therapeutics are obviously erythropoietin-stimulating agents (ESAs), which have played a critical role in this patient population. Hypomethylating agents can sometimes be utilized to control and manage the disease. We [also] see things like immunomodulatory, drugs, and steroids. So it's really going to be based on the patient presentation, what their characteristics tied to the disease are (the genetic abnormalities, etc).

PT Staff: What is the mechanism of action of luspatercept treatment?

Kirollos Hanna, PharmD, BCPS, BCOP, FACCC: So luspatercept has really been a significant drug that has made a big dent or impact on the anemias for these patients. When we look at patients with MDS, we know that there is an ongoing issue within their bone marrow. Sometimes it's not just about the production of red blood cells, but the quality of these red blood cells.

So when you look at ESA, it is mechanistically only focused on the production of more red blood cells; that therapeutic class doesn't really deal with the differentiation or maturation of the red blood cells. So if there is any type of abnormality within the red blood cell, an ESA is not going to do much to take care of that.

Now, when you look at something like luspatercept, mechanistically it is completely different. It kind of induces maturation, healthy maturation, in differentiation of these red blood cells. So it's not just about quantity, but it's more so about the quality of these red blood cells, and that mechanistically is the key difference between the 2.

PT Staff: What was the Real-World Retrospective Study of Non-Transfusion Dependent Patients with Myelodysplastic Syndromes Treated with Luspatercept? What was one of the most exciting findings from the study?

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Kirollos Hanna, PharmD, BCPS, BCOP, FACCC: We conducted a study (it’s a claims data-based study of patients who have had some type of luspatercept exposure). What we looked into—because what really stemmed the creation of the study is that, although we have seen FDA approvals, the majority of the data that's out there for luspatercept [is not real world data]; the real world evidence has been limited— was “What does the real world evidence looks like, from claims data?”

So what we did that in our study. We actually took claims data— we took about 240 patients who had a diagnosis of MDS, they could have had ring sideroblast positivity or that could have been unknown (the breakdown was about 50/50, in the grand scheme of things) and we identified an index date as the date that there was a first claim of luspatercept administration. We looked at what they required as a baseline, prior to the index date, and we also looked at how these patients did after exposure to luspatercept.

In our study, though, majority of patients (almost 100% of our patients) were exposed to prior ESA. And then, what we looked at was (what we define as transfusion independence) a rolling timeframe of these patients achieving transfusion independence once they were exposed to luspatercept. If we looked at this data based on real world evidence, we wanted to see if that is in line with the studies that have led to the approval of loose better stuff to begin with.

And it was actually very much so inline; almost 65% of patients who were exposed to luspatercept became transfusion independent over that rolling timeframe. So it's really helped us get a better understanding of its place in therapy, that it is effective based on real world data. It's in line with what we have seen in terms of FDA approvals, and it was something to help solidify its placed in therapy in the grand scheme of things. Now, obviously, we did look at claims data so there are some limitations with claims data. But again, this was a very exciting finding, and we're really excited to present it here at ASH.