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Investigating Therapies Targeting Cardiovascular Health in MDS With Diego Adrianzen Herrera, MD

In this interview from the 2023 American Society of Hematology (ASH) Annual Meeting, Oncology Data Advisor speaks with Dr. Diego Adrianzen Herrera, a Malignant Hematologist at the University of Vermont Medical Center, about his study investigating the impact of hypomethylating agents on cardiovascular disease risk for patients with myelodysplastic syndromes (MDS). Dr. Adrianzen Herrera explains the study's results and how they can be used to design future research around treatments targeting cardiovascular health in MDS.  

Oncology Data Advisor: Welcome to Oncology Data Advisor, I'm Keira Smith. Today, we're live at the ASH Annual Meeting, and I'm joined by Dr. Diego Adrianzen Herrera. Thank you so much for coming on today.

Diego Adrianzen Herrera, MD: Thank you for having me. I'm a Malignant Hematologist at the University of Vermont. I focus on myeloid malignancies mostly, but my research is focused on outcomes research and population-based analysis.

Oncology Data Advisor: Today, we're discussing your study about the impact of hypomethylating agents on cardiovascular disease risk among patients with myelodysplastic syndromes. For background, could you tell us, what is the association between MDS and cardiovascular disease?

Dr. Adrianzen Herrera: It's been known for a few years now that there is this pre-MDS condition called clonal hematopoiesis, which basically means that we find mutations in hematopoietic progenitor cells before the patient has any clinical manifestations. That has been linked with the risk of cancer, mostly myelodysplastic syndromes and acute leukemia, but it also has been significantly linked to cardiovascular disease—heart attacks, strokes, and things like that.

Building from that, since the precursor condition was linked to cardiovascular risk, I've been working for a few years now on understanding at the population level how MDS is associated with cardiovascular disease. In a study a few years ago, we demonstrated that MDS is an independent risk factor for cardiovascular disease. By analyzing Medicare data from Surveillance, Epidemiology, and End Results (SEER), which is a national registry across the US, we demonstrated the burden of cardiovascular disease is pretty high. About one in five patients with myelodysplastic syndromes will die of cardiovascular disease rather than from MDS or leukemia itself. That's sort of the background and how I got interested in that topic.

Oncology Data Advisor: That's a super helpful background for understanding the study. What were you investigating in this study with hypomethylating agents?

Dr. Adrianzen Herrera: Hypomethylating agents are probably one of the most important treatments we have for myelodysplastic syndrome. We don't use them in all patients, but we use them in those who have a little bit more significant disease, a little bit more aggressive disease. They have more low blood cell counts or higher risk of progression to leukemia, et cetera, and they're supposed to decrease the burden of the mutated cell clone, in theory. The hypothesis is, well, if those mutated cells are the ones that are going to the vasculature and causing inflammation, that leads to the cardiovascular events. Decreasing them should decrease the risk of cardiovascular events, in theory.

We wanted to understand if that actually happens at the population level with the caveat of doing population analysis. That's how we designed the study that we're presenting now, in which we basically took all individuals diagnosed with myelodysplastic syndrome in the SEER Medicare cancer registry. We came up with a propensity score to identify the probability of them being treated with these agents. Then we basically did a multivariable analysis with two different models to determine the effect after accounting for that probability of hypomethylating agents.

Oncology Data Advisor: Great. What were the results that you found with it?

Dr. Adrianzen Herrera: We found that there doesn't seem to really be any difference. The statistics are a little bit complex, but essentially, we accounted for all the appropriate factors. Obviously, older folks are going to have more heart attacks and strokes than younger folks. If someone already has a lot of medical issues to begin with—high blood pressure, diabetes, et cetera—they're probably going to have a high risk of cardiovascular disease as well. In the analysis, when we accounted for all of that, we found that the hypomethylating agents did not really affect the risk of someone having a cardiovascular event, whether that was a myocardial infarction, stroke, or a composite of both of those.

It's basically a negative finding, and we did that across two models. We also did another analysis. It's called a case crossover analysis in which each individual subject is its own control, but at different time period in the past, and we found similar results. We're basically presenting negative results, with the hope that will encourage others to say, well, this is still an unmet need because if the treatment that is supposed to be the best we have in myelodysplastic syndrome does not affect this outcome—which is significant, because again, one in five patients will die of cardiovascular events—then maybe we should start thinking of other strategies or other treatments to add or implement in our patients.

Oncology Data Advisor: Exactly. Along those lines, how can this knowledge be used to investigate alternative therapies or explore different avenues for this?

Dr. Adrianzen Herrera: Because of the nature of the field that I've been interested in, a lot of the time, patients with myelodysplastic syndrome are older and more complex because their blood levels are very low, and they have the stigma of having a blood cancer that is rare. Other specialties may not understand as well. What I find clinically is that they fall through the cracks a little bit in terms of their monitoring with their primary doctors.

The first thing I would like to bring up as a point is that even though someone's diagnosed with myelodysplastic syndrome, they should probably continue the best care they can for more common things like hypertension and diabetes. Those are things that we don't think about a lot in oncology, but again, this is a very particular population in which the cardiovascular morbidity and mortality are very high. Sometimes we fixate on the clones and the mutations, and we might be missing the opportunity to make sure that their blood pressure is well controlled or make sure that their diabetes is controlled, , which may have a bigger impact on their survival and quality of life. That's number one, and I just wanted to bring up that as a message.

Then number two, I would love to design or have some other folks in the field of myelodysplastic syndrome design studies or trials or some way to measure and study what interventions can actually change the cardiovascular health of these people. They are a very unique population in which, theoretically speaking at least, the cardiovascular events that they have are associated with these clones. I think it would be useful to check if the other treatments that we have for myelodysplastic syndromes affect or don't affect that risk. If they don't, such as what we're finding with hypomethylating agents, then should we start trying some agents that can do that.

Oncology Data Advisor: Has that been investigated before with other agents used in myelodysplastic syndromes?

Dr. Adrianzen Herrera: I don't think so. There's not a lot of focus on cardiovascular outcomes. Most of the studies in myelodysplastic syndrome focus on things like survival, transformation to leukemia, improvement of anemia, things like that. It's a little bit of a niche for me that I am very interested in this cardiovascular health, which is usually not reported in a lot of studies. Even though there are a lot of trials in myelodysplastic syndrome, and different drugs are tried, they don't usually reportthe rate of heart attacks, strokes, or cardiovascular mortality.

Oncology Data Advisor: That's definitely super important to explore.

Dr. Herrera: I would love to explore it more.

Oncology Data Advisor: Is there anything else you'd like to mention about your study or your research in this field?

Dr. Adrianzen Herrera: No, just thank you for having me. If someone listens and is interested in cardiovascular health among patients with myelodysplastic syndrome, just This email address is being protected from spambots. You need JavaScript enabled to view it.. I am definitely interested in how we can take this forward with more than just a retrospective analysis of the cancer registry.

Oncology Data Advisor: Definitely, and as as you continue your research in the field, we'd love to continue to hear more about this work. Well, thank you again for stopping by. It was wonderful meeting you.

Dr. Adrianzen Herrera: Thank you.

About Dr. Adrianzen Herrera

Diego Adrianzen Herrera, MD, is a Malignant Hematologist in the Department of Hematology and Oncology at the University of Vermont Medical Center (UVMC) and an Assistant Professor in the UVMC Larner College of Medicine. He specializes in the treatment of hematologic malignancies, including leukemia, lymphoma, multiple myeloma, and myelodysplastic syndromes. His research focuses on health disparities in blood cancer treatment, molecular targets and cellular therapies, mechanisms of clonal hematopoiesis and leukemogenesis, and treatments impacting cardiovascular health among patients with myelodysplastic syndromes.

For More Information

Adrianzen Herrera D, Sparks A, Gergi M, et al (2023). Impact of hypomethylating agents on cardiovascular disease risk among patients with myelodysplastic syndromes. Presented at: 2023 American Society of Hematology Annual Meeting. Abstract 549. Available at: https://ash.confex.com/ash/2023/webprogram/Paper185407.html

Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of Oncology Data Advisor. 


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