Novel Treatment Options for Patients With Myelodysplastic Syndromes

At the 2023 Lymphoma, Leukemia & Myeloma Congress in New York, Amer Zeidan, MBBS, MHS, Yale University, New Haven, Connecticut, discussed novel, clinically relevant updates in lower-risk and high-risk myelodysplastic syndrome (MDS). 

Transcript:

Hi everyone, my name is Amer Zeidan. I'm an associate professor of medicine at Yale University. It's a pleasure to be here [at the] Lymphoma, Leukemia, and Myeloma Congress in New York City. I talked about myelodysplastic syndromes (MDS), and the most recent updates that are relevant to clinical practice. 

I covered 3 main areas. The first area [was] updates in classification and response assessment in MDS. We covered differences between the [World Health Organization] (WHO) and the International Consensus Classification (ICC) 2020, as well as the efforts to harmonize these 2 systems into one classification system that can be used by everybody. Those efforts are led by the International Consortium for MDS.

We also talked about the problems with the current way response criteria have been used in high-risk MDS and the problems, for example, with marrow CR and stable disease as response criteria, and how that led to failure of drugs when they move from phase 1/phase 2 trials because they're promising, but when they go to phase 3 trials, they end up being negative results.

We [also] talked about how the new published criteria, the International Working Group 2023 criteria we published in Blood, will hopefully address some of this gap. We covered the new therapies for lower-risk MDS and how the landscape is changing with the new indication for luspatercept in the frontline setting based on the COMMANDS data.

Luspatercept was originally approached in the post-[erythropoiesis-stimulating agent] (ESA)-failure setting for patients who have ring sideroblasts with lower-risk MDS, who are transfusion dependent. However, the COMMANDS trial tested the drug in the frontline setting against ESA and in patients with or without ring sideroblasts. It was a positive trial, [where] 60% achieved transfusion independence that was durable, [at] 2 and a half years. And based on that, the FDA approved the drug as a first-line treatment for lower-risk MDS, in patients who might require red blood cell transfusions.

We talked about the promising data from the IMerge study, which looked at imetelstat, which is a first-in-class telomerase inhibitor. This was a trial that looked at the drug against placebo in the post-ESA-failure setting as well, and I think the data is quite good, [with] 40% transfusion independence in patients who are heavily transfusion-dependent at baseline, durable responses, significant increase in the hemoglobin by 3 and a half grams as a mean, as well as evidence of disease modification. The drug is currently in front of the FDA for consideration of approval. And if it's approved, it'll change the landscape of management of patients with lower-risk MDS.

And finally, we talked about management of high-risk MDS. Here, we did not have a lot of updates, but we focus on the importance of considering bone marrow transplantation, as well as the recent failures of some of the therapies that were combined with azacitidine. 

And importantly, being optimistic looking at the 2 phase 3 studies that are expected to report in the near future in the next few months, which are VERONA, which looked at adding venetoclax to azacitidine [for] high-risk MDS, as well as STIMULUS-MDS2, which looked at adding sabatolimab, which is a TIM-3 inhibitor to azacitidine, as well as other promising agents in both lower risk and high risk MDS.

Source:

Zeidan A. Untangling Classification, Risk Assessment and Exploring Treatment Options in Low and High Risk MDS. Presented at Lymphoma, Leukemia & Myeloma Congress; October 18-21, 2023. New York, NY