Effective Risk Stratification for Patients With Myelodysplastic Syndromes

At the 2023 Great Debates & Updates in Hematologic Malignancies conference in New York, New York, Amer Zeidan, MBBS, MHS, Yale New Haven Health, New Haven, Connecticut, discussed effective risk stratification among patients with myelodysplastic syndromes (MDS), including recent updates in classification, prognostication, and management.  

Transcript: 

Hi everyone. My name is Amer Zeidan. I'm an associate professor of medicine at Yale University, and I had the pleasure of speaking today at the meeting in New York City, the Great Debates in Hematologic Malignancies, where I discussed updates in the classification, prognostication, as well as management of myelodysplastic syndromes.

My talk covered 3 main aspects. First was the updates in the classification of MDS, as well as the prognostication and risk tools. The second aspect was covering the updates in management of lower-risk MDS, and the last part was updates on the management of high-risk MDS disease.

We started by discussing the importance of making sure that the diagnosis of MDS is a correct one, because myelodysplasia can result from different conditions, drug effects, and other blood conditions [which] can cause dysplasia so you have to make sure it's really myelodysplastic syndromes.

Then we discussed the classification and the updates from the WHO and the ICC, the International Consensus Classification of 2022. We talked about issues that can come in practice from using 2 different classifications, and how it's important to have a harmonized, hopefully unified [single] classification system in the near future. But until then, we have to work with these 2 classifications and we need to understand the differences in terms of patients being diagnosed with MDS or AML.

In terms of the risk tools, we discussed the incorporation of molecular alterations and the commonly used prognostic tools such as the IPSS-M [International Prognostic Scoring System- Molecular] and the molecular IPSS. This has been published in 2022. It started to be more used, I think, not only in academic centers, but in the community at large, but it requires obtaining a large number of molecular alterations through standardized panels.

Then we started talking about the management of patients with lower-risk and high-risk MDS. For lower risk, the main updates have been the use of luspatercept for patients with lower-risk MDS who have ring sideroblasts but have not responded to ESAs [erythropoietin-stimulating agents]. 

We discussed the MEDALIST Trial that led to the approval of luspatercept, as well as the COMMANDS Trial, which has been press-released as a positive trial, which looks at luspatercept in the frontline setting. 

We also discussed the use of imetelstat, which is a first-in-class telomerase inhibitor for also lower risk MDS after ESA failure for patients who are transfusion-dependent, with nice data in a phase 2 trial with transfusion independence in the range of 40%. But importantly, also a positive press release for the phase 3 trial called the IMerge and those data hopefully will be presented in the near future.

In high-risk MDS, we discussed some of the most recent updates on the combination therapies, including venetoclax, sabatolimab, and magrolimab, all of which have been combined with azacitidine in multiple randomized phase 3 trials. All of them are ongoing and have completed accrual. We are waiting for the results.

Lastly, we emphasized the importance of considering transplant even for older patients with high-risk MDS because it's the only potential way to cure patients, as well as trying to look for alterations that might help in decisions for therapy. For example, having IDH mutations could offer an option after HMA failure.

Source: 

Zeidan, A. Effective risk stratification and expert treatment selection advice for patients with myelodysplastic syndromes. Presented at Great Debates & Updates in Hematologic Malignancies Conference; April 13-15, 2023; New York, NY.