Study: olutasidenib is highly effective in certain patients with myelodysplastic syndrome

MIAMI, FLORIDA (July 25, 2025) – The targeted drug olutasidenib is highly effective in certain patients with myelodysplastic syndrome (MDS), a condition considered incurable without transplantation, according to a new clinical study led by researchers at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine.

Patients enrolled in the study had tumors with mutations in the gene for isocitrate dehydrogenase-1 (mIDH1), the target of olutasidenib.

The findings are leading to changes in care for patients with MDS, who often must undergo repeated blood transfusions and have few treatment options, largely limited to conventional chemotherapy or transplantation with bone marrow or blood stem cells.

“We saw really quite remarkable outcomes in a very high-risk MDS population, not only in response rates, but also in blood count improvement, long duration of response and improved overall survival,” said Sylvester physician-scientist Justin Watts, M.D., who led the study.

The findings were published July 18 in Blood Advances.  

Common Targets

Watts and colleagues have previously tested olutasidenib in patients with acute myeloid leukemia (AML) who had “refractory” disease that did not respond to conventional treatment or who had relapsed.

Their research led to the 2022 approval of olutasidenib for certain patients with IDH1-mutant AML, which occurs in about 10% of AML. After that success, Watts and his team began to focus closely on testing the drug in MDS, a related condition that often progresses to AML.

IDH-1 mutations also occur in MDS, at a frequency of 3 to 5%.

In the current study, the researchers tested olutasidenib in 22 MDS patients with IDH1-mutant tumors. All patients were classified with intermediate to very high-risk disease, with 86% being high or very high risk.

Patients received either olutasidenib alone or in combination with azacitidine, the standard chemotherapy treatment for MDS. That choice was largely at the discretion of their physicians, as older, frailer patients are often poor candidates for harsh chemotherapy.

Patients included seven newly diagnosed individuals and 15 people who had relapsed or refractory disease.

The team reported that 59% of the study’s population responded to the new treatment, and a high proportion previously dependent on transfusions no longer needed them.

The median overall survival rate was 27.2 months in the entire group of patients, with 16.3 months in people with relapsed/refractory disease. Olutasidenib was shown to be safe with few associated side effects.

These are strong outcomes compared to historical studies of survival rates in MDS, said the researchers. For instance, one previous study found only a 5.6-month survival rate in high-risk relapsed or refractory MDS patients treated with conventional therapy. The results also align with studies showing the potential effectiveness of a different inhibitor of mIDH1, the drug ivosidenib.

 “Both are exceptional drugs,” said Watts.

He and his team reported on the data previously at international meetings, which has already led to changes in treatment standards.

Olutasidenib with or without azacitidine is now recommended in the National Comprehensive Cancer Center Network Guidelines for certain patients with IDH1-mutant MDS, including as a front-line treatment in combination with azacitidine for higher-risk patients.

The study is part of a larger effort by Watts and other Sylvester researchers to investigate a suite of new agents against blood cancers, including drugs targeted against other driver mutations linked to disease.

Sylvester enrolls close to 100 leukemia patients each year in more than 25 active clinical trials, about half of which are led by Sylvester. Options include triple combination therapies, multiple targeted therapies, and immunotherapy approaches.

“This is a multifaceted and complex operation,” said Watts, who believes that olutasidenib may be capable of inducing highly durable responses in some AML and MDS patients.

He and his team had earlier noticed that some AML tumors that responded exceptionally well to olutasidenib seemed to resemble MDS. These AML tumors had only a few cancer-causing mutations, other than in IDH1.

One of these AML patients has now been in remission for nine years since initiating olutasidenib treatment, a time frame consistent with a cure, and she continues today on olutasidenib without any evidence of detectable disease by deep sequencing analysis. This patient case was reported July 1 in Nature Precision Oncology.

Watts and his team are now taking a closer look at AML and MDS patients with longer-term responses to olutasidenib. “We’re trying to get a more precise signature of who these patients are. How can we tell which patients are going to do well with this therapy and have longer-term remissions?” said Watts. “That’s the next paper.”

Read more about Sylvester research on the InventUM blog and follow @SylvesterCancer on X for the latest news on its research and care.

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