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New Developments in Risk Stratification and Management of High-Risk and Low-Risk MDS

Featuring Amer Zeidan, MBBS

 

At the 2023 Great Debates & Updates in Hematologic Malignancies Meeting in Boston, Massachusetts, Amer Zeidan, MBBS, Yale University School of Medicine, New Haven, Connecticut, speaks on recent developments in risk stratification and treatment management among patients with high-risk and low-risk myelodysplastic syndromes (MDS). 

Transcript: 

Hello, my name is Amer Zeidan. I'm an associate professor of medicine at Yale University and the director of the leukemia program at Yale. I spoke at the Great Debates and Updates [in Hematologic Malignancies] meeting in Boston about the risk stratification in myelodysplastic syndromes, as well as updates in the management of lower and high-risk MDS.

The main aspects of my talk were covering some of the recent developments in terms of risk stratification and classification for myelodysplastic syndromes. We covered the new classification systems by the [World Health Organization] (WHO) and the International Consensus Classification (ICC) that were published in the year 2022. 

We discussed how MDS now is classified both as genetically defined groups such as those associated with SF3B1, TP53, or deletion 5Q, as well as morphologically defined groups such as the WHO-defined MDS with fibrosis or hypoplastic MDS and the new group of MDS/[acute myeloid leukemia] (AML) overlap, which is under the ICC 2022 classification.

We also talked about issues related to risk stratification, especially the introduction of the molecular [International Prognostic Scoring System] (IPSS). Historical risk stratification of MDS used cytogenetics, [platelet] count, and cytopenias, but most recently, the molecular IPSS also used or integrated the molecular assessment as part of the risk stratification, which led to improved accuracy. It's becoming the most widely used tool to assist prognosis in MDS.

We also covered some of the recent therapeutic advances. Some of the most impressive advances in MDS in the year 2023 [were] actually in lower-risk MDS. We talked about some of the new data from [the American Society of Clinical Oncology annual meeting] (ASCO) and [the European Hematology Association meeting] (EHA) focusing on 2 drugs: imetelstat and luspatercept. Luspatercept is a transforming growth factor (TGF) inhibitor that is approved currently after [erythropoiesis-stimulating agents] (ESA) failure in lower-risk transfusion-dependent anemia and in patients who have ring sideroblasts.

We discussed recent data from the COMMANDS trial, which tested luspatercept in the frontline setting and in patients with and without ring sideroblast, and it was a positive trial. We talked about imetelstat, which is a first-in-class telomerase inhibitor, which was also shown in a phase 3 trial after ESA failure to lead to significant transfusion independence rates among patients with lower-risk MDS who are transfusion-dependent and anemic. Both of those drugs are currently in front of the FDA and they are being considered for approval. They could potentially change the standard of care in the management of lower-risk MDS.
On the high-risk MDS front, the developments have not been as great so far. Unfortunately, the major update has been the negative data from the magrolimab [ENHANCE] phase 3 trial. That came in a press release. We don't have those details yet, but some of the other phase 3 [trials] are still ongoing, with venetoclax and sabatolimab and tamibarotene. We're hoping to see results later this year or early 2024. Hopefully, we can see some improvement in the landscape of high-risk MDS as well. Thank you.

 


Source: 

Zeidan, A. Effective Risk Stratification and Expert Treatment Selection Advice for Patients with Myelodysplastic Syndromes. Presented at the Great Debates and Updates in Hematologic Malignancies Meeting; August 17-19, 2023; Boston, Massachusetts. 
 

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