Subanalysis Supports Imetelstat for Transfusion-Dependent Low- to Intermediate-1–Risk MDS


Mikkael A. Sekeres, MD, discusses the FDA approval of imetelstat for patients with low- to intermediate-1–risk MDS, highlighting data from a subanalysis.

Mikkael A. Sekeres, MD, MS

Mikkael A. Sekeres, MD, MS

Findings from a subanalysis further support the use of imetelstat (Rytelo) in the treatment of patients with transfusion-dependent low- or intermediate-1–risk myelodysplastic syndrome (MDS), according to Mikkael A. Sekeres, MD, who noted treatment with the agent led to significant rise in hemoglobin levels vs placebo. Data from this analysis on the effect of imetelstat on red blood cell (RBC)-transfusion independence in the absence of platelet transfusions or myeloid growth factors, as well as the data which supported the FDA approval of imetelstat, were derived from the phase 3 IMerge trial (NCT02598661).1,2

IMerge demonstrated a significant improvement in RBC transfusion independence rates, with 28% (95% CI, 20.1%-37.0%) of patients in the imetelstat group (n = 118) vs 3.3% (95% CI, 0.4%-11.5%) of patients in the placebo group (n = 60) experiencing RBC transfusion independence for at least 24-weeks (P < .001). The subanalysis also found that, among responders, the median hemoglobin level rise was 3.6 g/dL in the imetelstat arm vs 0.8 g/dL in the placebo arm for at least 8-weeks; rises were 5.2 g/dL vs 1.7 g/dL for 1-year or more, respectively.1,2

“Following imetelstat’s approval for patients who are transfusion dependent with lower-risk MDS, we finally have another tool in our tool set for how to treat these patients,” Sekeres said in an interview with OncLive®. “Findings [from IMerge] will help bolster [the] approval by demonstrating that not only do patients become transfusion independent, but they also have a rise in their hemoglobin levels irrespective of whether they have other abnormalities of other blood counts.”

In the interview, Sekeres discussed the FDA approval of imetelstat for patients with low- to intermediate-1–risk MDS and highlighted the importance of this approval for patients who have transfusion-dependent anemia requiring RBC transfusions or who are not eligible for erythropoiesis-stimulating agent (ESA) treatment.

Sekeres is a professor of medicine as well as the chief of the Division of Hematology in the Leukemia Section at the University of Miami Sylvester Comprehensive Cancer Center in Florida. You can hear more from Sekeres about imetelstat on OncLive On Air, a podcast from OncLive.

OncLive: What key efficacy findings have been reported from IMerge?

Sekeres: The telomerase inhibitor imetelstat was explored in patients [with] lower risk MDS who are already dependent on RBC transfusions; the primary end point of [IMerge] was to assess whether imetelstat compared with placebo led to higher rates of transfusion independence in these patients.

In the initial study, 39.8% of patients who were treated with imetelstat achieved transfusion independence lasting at least 8 weeks compared with 15.0% of patients who were treated with placebo. As you look over time at patients who not only had transfusion independence lasting 8 weeks, but out to 16 weeks or even 24 weeks, the efficacy of imetelstat held. Approximately one third of patients overall had durable transfusion independence [for at least 24 weeks] when they were treated with imetelstat compared with [3.3% of] patients who were treated with placebo. There were very durable, impressive rates of transfusion independence for patients treated with imetelstat compared with placebo.

What were the key findings from the subanalysis?

This follow-up analysis looked at patients who were responding to imetelstat and looked at a couple of factors. The first was if patients had an improvement in their hemoglobin levels—not only did they become transfusion independent, but how high did their hemoglobin levels go? On average, hemoglobin levels improved by approximately 3 g/dL; that’s a substantive improvement in hemoglobin levels in patients achieving transfusion independence.

The second aspect of this follow-up analysis looked at whether these achievements in hematologic improvement were separate from patients who required [myeloid] growth factors or those who needed transfusions for low platelet counts. It turns out they were. Whether or not [there were] other abnormalities of cell lines, improvement in hemoglobin and transfusion independence rates were the same.

What is the significance of the approval of imetelstat for this patient population?

We have had a ‘drug desert’ that has occurred for over a decade [regarding] new treatments for patients with lower-risk MDS. For those who have anemia, we typically start [treatment] with ESAs. If they have a del(5q) abnormality, we will move to lenalidomide [Revlimid]. There are also approvals for luspatercept-aamt [Reblozyl], both in the upfront and the subsequent setting after patients have been exposed to ESAs. That drug works predominantly in patients who have either a spliceosome mutation or ring sideroblasts.

For those patients who don’t have a spliceosome mutation, ring sideroblasts, or del(5q) abnormalities, the only thing we have left are hypomethylating agents. With imetelstat, we have another option to treat patients, either before or after they’re exposed to hypomethylating agents.

I do believe that imetelstat is going to be explored not just in lower-risk MDS, but also in patients with higher-risk MDS. I anticipate that combinations of drugs with imetelstat will also be explored.

What is key to note about the safety profile of imetelstat?

Imetelstat is associated with treatment-related cytopenias. As the drug is used in patients, doctors can give patients drug holidays that are limited to see if blood counts recover. They can use supportive measures such as [myeloid] growth factors or lower the dose of imetelstat.


  1. FDA approves imetelstat for low- to intermediate-1 risk myelodysplastic syndromes with transfusion-dependent anemia. FDA. June 6, 2024. Accessed July 10, 2024.
  2. Zeidan AM, Santini V, Platzbecker U, et al. Efficacy of imetelstat on red blood cell (RBC)-transfusion independence (TI) in the absence of platelet transfusions or myeloid growth factors in IMerge. J Clin Oncol. 2024;42(16):6566. doi:10.1200/JCO.2024.42.16_suppl.6566
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