Dr Elli Papaemmanuil Discusses Molecular Profiling of MDS, Use of Precision Medicine

Although we are still very early in the process of understanding biological pathways of myelodysplastic syndromes (MDS), our ability to stratify patients on the basis of their gene mutations will give us a tool in the short term that will enable us to tailor treatments based on the patients who are most at need, said Elli Papaemmanuil, PhD, assistant professor in Computational Oncology, Memorial Sloan Kettering Cancer Center.

Papaemmanuil led a plenary session at the 2022 European Hematology Association (EHA) Congress, titled, “Molecular Classification and Prognostication in MDS.”

Transcript

As MDS are characterized by their heterogeneity, can you discuss current understanding and how disease subtypes differ by severity and response to treatment?

So, myelodysplastic syndromes are truly a spectrum of myeloid disorders, and they can be very diverse from one another, ranging from patients who have very-low-risk disease, and these are the types of patients who clinically we want to manage with supportive therapy—they can go on to live up to 10 years—and then on the other spectrum, we have patients with really-high-risk disease. Those patients require high-intensity therapies and can live up to a few months to a year and often can progress rapidly to more acute forms of the disease.

This heterogeneity and the fact that patients can have a very broad spectrum of both clinical presentation and outcomes is something that challenges how to optimally manage and treat patients in the clinic. So, we really need tools and measurements that allow us to identify which patients are likely to be low risk or high risk so that we can cater our treatment decisions toward each patient's profile.

How can current knowledge on gene mutations and biological pathways in MDS influence use of precision medicine, and what further progress may be observed here?

So, we're at the very early days. The genes that are mutated in MDS have only been discovered over the past 5 to 10 years. This enables us to understand the underlying biology of MDS, and in time what we really want to enable is the development of drugs that target those biological pathways.

In the short term, our ability to stratify patients on the basis of their gene mutations will give us a tool that will enable us to tailor treatments based on the patients who are most at need. What this means is that we will minimize toxicities in patients that have low-risk disease, but we will be able to intervene early in those patients at higher risk of disease progression and disease transformation.

In the long term, we will be able to link the biological pathways that result in high-risk disease, and that will enable us to develop therapeutic strategies that target those very pathways. So, that's where we can have both the short- and long-term benefit by consideration of the molecular profiles of MDS patients.