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Imetelstat Produces RBC Transfusion Independence in Lower-Risk Myelodysplastic Syndromes

February 29, 2024

March 2024

Thomas R. Collins

Thomas R. Collins is a medical journalist based in West Palm Beach, Florida.

The competitive telomerase inhibitor imetelstat produced prolonged independence from red blood cell (RBC) transfusions in a considerable number of patients with lower-risk myelodysplastic syndromes (MDS) who were ineligible for, had relapsed on, or been refractory to erythropoiesis-stimulating agents (ESA), according to new phase III findings published in The Lancet.

The results from the IMerge trial point to the prospect of a new therapy for patients with MDS who struggle with available options. Patients with lower-risk MDS often become reliant on RBC transfusions, and ESAs are the standard firstline treatment. Many patients, however, either don’t respond to ESAs or lose their response in about two years. The therapy has been submitted for approval to the U.S. Food and Drug Administration and European Medicines Agency.

“Apart from luspatercept for ring sideroblast-positive MDS, there is nothing to offer, especially not for patients with a high transfusion burden like in the IMerge trial,” who required at least four units of RBCs over an eight-week period in the 16 weeks leading to randomization, said Uwe Platzbecker, MD, professor of hematology at the University of Leipzig Medical Center in Germany and first author on the study. As such, there is a “high medical need” for other therapy options.

Imetelstat is a first-in-class oligonucleotide that can competitively inhibit telomerase activity — which is upregulated in hematologic malignancies — by binding to TERC, the telomerase component of RNA.

“Telomerase is an attractive target, as it is highly expressed and reactivated in the majority of myeloid neoplasms and absent in most cell types, including healthy hematopoietic cells,” Dr. Platzbecker said.

In the study, researchers enrolled patients with MDS who had not responded to an ESA, had relapsed on an ESA, or were not eligible to receive an ESA. They needed to have received at least four RBC units over eight weeks within 16 weeks before being randomized; the median prior RBC transfusion burden was six units over eight weeks. This burden was more than six units over eight weeks in 47% of the patients. To be enrolled, patients could not have received lenalidomide or a hypomethylating agent and could not have del(5q) MDS.

Researchers found that 47 of the 118 patients (40%) receiving imetelstat achieved transfusion independence of at least eight weeks, compared to nine of 60 (15%) in the placebo group. Eighteen percent of patients in the imetelstat group achieved transfusion independence of at least one year, compared to 2% in the placebo group.

The patients who hit the eight-week transfusion-independence mark went on to be independent from transfusions for a median of 51.6 weeks, researchers reported. Of the nine in the placebo group who remained transfusion independent for eight weeks, they remained so for just 13.3 weeks.

Transfusion independence tended to be continuous over time, researchers found, with 83% of patients having a single continuous RBC transfusion-independence period.

Eight-week transfusion independence was achieved in 33 of 73 patients (45%) with ring sideroblasts, and in 14 of 44 (32%) without ring sideroblasts, compared to 19% and 9%, respectively, in the placebo group.

When researchers looked at prior transfusion burden, they found that 28 of 62 patients (45%) of those in the imetelstat group who had received four to six units over eight weeks achieved transfusion independence for eight weeks, while 34% of patients who had received more than six units achieved this.

Those receiving imetelstat who achieved eight-week or 24-week infusion independence had sustained and meaningful improvement in fatigue scores, though this relationship wasn’t seen for the placebo group, researchers reported.

The most common grade 3-4 treatment-emergent adverse events (AEs) in the imetelstat group were neutropenia, seen in 68%, with a median duration of 1.9 weeks, and thrombocytopenia, seen in 62%, with a median duration of 1.4 weeks. Most of these events occurred within the first three treatment cycles. Severe clinical consequences of neutropenia and thrombocytopenia — grade 3-4 bleeding events, grade 3-4 infections, and febrile neutropenia — were similar in patients treated with imetelstat and placebo. About half of patients in the imetelstat group had dose reductions — mostly because of neutropenia or thrombocytopenia, but the rate of transfusion independence in these patients was consistent with rates in the overall imetelstat population, researchers found. Nineteen (16%) patients receiving imetelstat and none receiving placebo discontinued treatment because of AEs.

“IMerge phase III results,” researchers said, “validate the observations from the phase II part and show that imetelstat provides clinically significant benefit to a heavily transfusion-dependent [lower-risk] MDS patient population.”

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


Platzbecker U, Santini V, Fenaux P, et al. Imetelstat in patients with lower-risk myelodysplastic syndromes who have relapsed or are refractory to erythropoiesis-stimulating agents (IMerge): a multinational, randomised, double-blind, placebo-controlled, phase 3 trial [published online ahead of print, 2023 Dec 1]. Lancet. doi: 10.1016/S0140-6736(23)01724-5.


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