Imetelstat Updates For Lower-Risk MDS

At the 2025 European Hematology Association (EHA) conference, researchers shared results from the IMerge clinical trial that show how imetelstat (Rytelo, Geron Corporation) can help people with MDS who have anemia and cannot be treated with other therapies. People with  myelodysplastic syndromes (MDS) develop anemia because there are too many abnormal cells crowding out healthy red blood cells. Their anemia often needs to be treated with red blood cell transfusions. Anemia can cause fatigue, shortness of breath, and weakness and regular blood transfusions can affect a person’s quality of life. 

The first-line treatment for MDS is a class of  medications that  target erythropoietin, which is a hormone that controls red blood cell production. These are called erythropoiesis-stimulating agents (ESAs). However, some people have high serum erythropoietin levels, which makes ESAs less effective. Others may no longer respond to ESAs over time.

Imetelstat is an oligonucleotide telomerase inhibitor. It stops the growth of abnormal cells in people with MDS by blocking the telomerase enzyme. 

Can imetelstat help patients with lower-risk MDS who are ineligible for other treatments?

The IMerge clinical trial included 210 people with MDS. The participants were grouped based on different characteristics: 

• No prior ESA or other therapies with high serum erythropoietin levels of more than 500 mU/mL (13 people)
• Prior ESA treatments with serum erythropoietin levels of less than 200 mU/mL (112 people)
• Prior ESA treatments  with serum erythropoietin levels of 200 to 500 mU/mL (43 people)
• Prior ESA treatments with serum erythropoietin levels of more than 500 mU/mL (42 people) 

The participants were grouped this way because high serum erythropoietin levels can be a sign that a person will not benefit from ESA therapy.

The study showed that imetelstat provided benefit regardless of serum erythropoietin levels. For the 13 people with no prior ESA and high serum erythropoietin levels, 54% did not need an RBC transfusion for at least 8 weeks. The median time without a transfusion was almost 43 weeks. This group also saw other improvements, with 38% having a hemoglobin level rise by 1.5 g/dL or more for 8 weeks or more.    

Benefits were also observed after ESA treatment, regardless of erythropoietin level

The analysis also looked at patients who had already received ESA therapy. Among those with high serum erythropoietin levels, imetelstat still showed effectiveness. This included achieving transfusion independence and hematologic improvement even in those with disease that did not respond to ESAs.

This is important because it confirms that imetelstat is useful not only as a first treatment for those ineligible for ESAs but also later for those who previously tried them.

Imetelstat works in patients without ring sideroblasts

Another factor that influences treatment response in MDS is if ring sideroblasts (RS) are present. Ring sideroblasts are immature red blood cells with a iron deposits that form a ring around the nucleus, which can be found in some people with MDS. Many available treatments, including luspatercept, work better in patients who have ring sideroblasts.

However, most people with lower-risk MDS don’t have ring sideroblasts. In the IMerge study, 78 people without ring sideroblasts were treated with imetelstat. Of those, 33% achieved at least 8-week transfusion independence, and 13% remained transfusion-free for at least 1 year.

Patients without ring sideroblasts typically have fewer treatment options. The results show that imetelstat can provide meaningful benefit in this group.

Lower transfusion burden is also linked to response

In patients with RS-negative disease and a low transfusion burden, 36% achieved hematologic improvement with imetelstat. In those with a high transfusion burden, 22% had a major response and 40% had a minor response. These improvements included either long periods without transfusions or significant reductions in the number of transfusions needed.

This suggests that imetelstat may help regardless of how many transfusions patients need when they start treatment, and may lead to improved quality of life.

Summary

Imetelstat is showing benefit in a range of MDS cases: those with high serum erythropoietin levels, those who failed ESA therapy, and those with RS-negative disease. It can help patients become less dependent on transfusions and improve red blood cell production. These findings support its use across different subgroups of lower-risk MDS.

Keep reading more MDS updates with the HealthTree News site!

READ MORE ARTICLES

Sources: 

• Outcomes of Imetelstat Therapy in RS-Negative LR-MDS from the Pooled IMerge Study Populations

• Outcomes with Imetelstat by Serum Erythropoietin Levels in Patients with LR-MDS Who Were Treatment Naïve or Who Had Prior Treatment with Erythropoiesis-Stimulating Agents