Guillermo Garcia-Manero, MD, MD Anderson Cancer Center, Houston, Texas, discussed the various treatment options available for patients with low-risk and high-risk myelodysplastic syndrome (MDS).

“We've seen quite a bit of progress in low-risk disease. I think we are at the edge of getting some positive results in high-risk MDS. We will basically now see quite a bit of progress in the development of oral hypomethylating agents such as the decitabine-cedazuridine. There's a compound known as ASTX030 that is coming. That is the [combination of] [oral cedazuridine and azacitidine],” explained Dr Manero.

This research was presented at the 2024 Annual Society of Hematologic Oncology (SOHO) meeting in Houston, Texas.

Transcript:

Good morning. My name is Guillermo Garcia-Manero from the Department of Leukemia at MD Anderson Cancer Center in Houston, Texas. I'm going to give you a summary of what we presented at the annual meeting of the Society of Hematology Oncology (SOHO) during the first week of September 2024 here in Houston.

Next, we move to high-risk MDS. This is not yet that positive. Over the years we've been working on a backbone of a hypomethylating agent (HMA), either azacitidine or decitabine. In 2020, we led the approval of oral decitabine-cedazuridine. These are the oral hypomethylating agents. This drug, in my opinion, appears to be a little bit more potent than decitabine.

We have been able to combine it, for instance, with BCL2-inhibitor venetoclax with very high rates of response. That said, we've not been able to formally approve a doublet that is shown to be superior to single agent azacitidine.

In 2022 to 2023, we saw a list of negative trials including combinations with CD47 antibodies, combination with [ ] inhibitors, combinations with drugs that interfere with P53 protein like a [ ] compound and most recently inhibitors of TIM-3 such as sabatolimab. This has been a little bit disappointing to us because we work very hard, and we really need combination in frontline high-risk MDS. There are [several] studies indicating that the combination of a hypomethylating agent plus venetoclax, the BCL2 inhibitor that is the standard of care in acute myeloid leukemia (AML), is also active in myelodysplastic syndrome.

We are all eager and waiting for the results of a trial known as the VERONA trial that should be, we hope early next year, that compared azacitidine with venetoclax versus azacitidine. That study is going to be fundamental in our field. If it's positive, it will be our next standard of care. If it's negative, I think we'll have to really think about next generation of trials in high-risk disease. We're transplanting more than ever; we see very positive data from multicenter groups from MD Anderson in terms of outcomes of patients with MDS being transplanted in good responses. That's also quite optimal.

We're seeing some progress also in this aspect of targeted approaches for subset of patients with mutations. We saw the recent approval of ivosidenib for IDH1-mutated relapsed MDS. We have some positive data also with [ ], and the audience needs to remember that some of these patients may be FLT3-mutated. Although none of these targeted agents are formally approved for MDS, they are quite active and may help you particularly in second-line disease where we don't really have very active compounds.

In summary, we've seen quite a bit of progress in low-risk disease. I think we are at the edge of getting some positive results also in high-risk MDS. We will basically now see quite a bit of progress in the development of oral hypomethylating agents such as the decitabine-cedazuridine. There's a compound known as ASTX030 that is coming. That is the [oral cedazuridine and azacitidine]. If we are successful next year with all this, we will really have to focus on the development of targeted approaches and drugs for, or studies for patients with HMA failure.

With that, I want to thank you for your attention. Thank you very much.

Source:

Manero G. Resetting Standards in MDS: New Principles for Integrating Innovative Therapy Into Risk-Adapted Decision-Making. Presented at the 2024 Society of Hematologic Oncology meeting. Houston, Texas; September 4-7, 2024.