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Imetelstat May Provide New Treatment Option for MDS Refractory to ESAs

June 5, 2023

Mid-July 2023

Ruth Jessen Hickman, MD

Ruth Jessen Hickman, MD, is a freelance medical and science writer based in Bloomington, Indiana.

Imetelstat may provide a new treatment approach in patients with lower-risk myelodysplastic syndromes (MDS) who require regular transfusions to treat anemia but are refractory or relapsed to erythropoiesis-stimulating agents (ESAs), according to interim results of the phase III global IMerge study. Amer Zeidan, MBBS, of Yale University in New Haven, Connecticut, presented the results at an American Society of Clinical Oncology (ASCO) Annual Meeting oral abstract session on June 2.

“Lenalidomide and luspatercept are treatment options after ESA failure,” said Dr. Zeidan. “But they are most effective in specific subpopulations – patients with del5q and ring sideroblasts/SF3B1 mutations, respectively. This leaves many patients with ... limited therapeutic options.”

Imetelstat, a telomerase inhibitor, specifically targets malignant clones with abnormally high telomerase activity, enabling recovery of hematopoiesis. During his presentation, Dr. Zeidan noted, “Phase II of IMerge showed a 40% transfusion independence rate and durable transfusion independence.”

Included in this interim analysis were 178 heavily transfusion-dependent patients, who were randomized 2:1 to receive imetelstat or placebo, respectively. No patients had received prior therapy with lenalidomide or hypomethylating agents. Patients were stratified by their current transfusion burden and their International Prognostic Scoring System risk category.

The study met its primary endpoint: about 39.8% of patients receiving imetelstat did not require transfusions for at least an eight-week consecutive period during the study, in contrast to 15.0% of those receiving placebo. This difference held across various subgroups, including patients without ring sideroblasts, a subgroup without a treatment option approved by the U.S. Food and Drug Administration after ESA failure.

Dr. Zeidan said, “Importantly, the response was durable. The median duration for those patients who achieved eight-week transfusion independence was 51 weeks compared with 13 weeks with placebo.” He underscored that the initial baseline hemoglobin level for patients was around 8 g/dL, but by the end of the study, patients on imetelstat had an impressive median hemoglobin rise of 3.6 g/dL. Patients receiving imetelstat also had fewer transfusions when analyzed over time.

Dr. Zeidan noted the most common adverse events (AEs) were grade 3 to 4 thrombocytopenia and neutropenia, consistent with earlier work, and non-hematologic AEs were generally low grade. The hematologic events, although common, could largely be handled by lowering or temporarily interrupting treatment and providing growth factor support, and most were short in duration. Given liver toxicity was reported in earlier trials at higher doses, they found no drug-induced liver injury.

Dr. Zeidan also explained that imetelstat may have disease-modifying activity. The team compared myeloid gene mutations at baseline and after treatment and found a significant reduction in the variant allele frequency (VAF) in the four most commonly mutated genes: SF3B1, TET2, DNMT3A, and ASXL1. He added, “The reduction in SF3B1 [VAF] was also associated with higher hemoglobin level as well as prolonged duration of transfusion independence, again suggesting disease modification with this agent.”

Dr. Zeidan concluded that imetelstat provides "a clinically meaningful benefit in patients [with MDS] who are transfusion dependent.”

Any conflicts of interest declared by the authors can be found in the original abstract.


Zeidan AM, Platzbecker U, Santini V, et al. IMerge: Results from a phase 3, randomized, double-blind, placebo-controlled study of imetelstat in patients (pts) with heavily transfusion dependent (TD) non-del(5q) lower-risk myelodysplastic syndromes (LR-MDS) relapsed/refractory (R/R) to erythropoiesis stimulating agents (ESA). Abstract 7004. Presented at the 2023 American Society of Clinical Oncology, June 2, 2023; Chicago, Illinois.


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