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Phase 3 Results Offer Hope for Patients With Myelodysplastic Syndromes

December 04, 2023
by Michael Masciadrelli

For people living with certain blood cancers, including lower-risk myelodysplastic syndromes (LR-MDS), there are limited effective treatment options. This is especially true for MDS patients who are red blood cell transfusion-dependent (RBC-TD) and who do not respond to, or are not eligible for, the treatment typically used to stimulate bone-marrow to make red blood cells. MDS are a group of cancers in which immature blood cells in the bone marrow do not mature or become healthy blood cells, causing low blood counts and subsequent complications.

In a phase 3 trial known as IMerge, researchers sought to compare the rate of RBC transfusion independence (RBC-TI) with imetelstat — which aims to inhibit the activity of the corrupted telomerase enzymes related to the cancer — versus the RBC-TI rate with placebo, in patients with RBC-TD LR-MDS. Imetelstat is under review by the U.S. Food and Drug Administration for approval to treat transfusion-dependent anemia in patients with lower risk MDS who cannot have erythropoiesis-stimulating agents.

Published in The Lancet on December 1, the trial results showed that transfusion independence (TI) for at least eight consecutive weeks was significantly higher for patients taking imetelstat, with a median TI duration approaching one year. Hemoglobin levels in imetelstat-treated patients also increased significantly over time compared to the patients on the trial who had placebos.

“Deep anemia requiring regular transfusions in patients with lower-risk MDS is a major driver of increased morbidity and mortality for these patients, as well as a compromised quality of life, and increased health care utilization and costs,” said senior author of the study Amer Zeidan, MBBS, associate professor of medicine (hematology) at Yale School of Medicine and director of hematology early therapeutics research at Yale Cancer Center.

To be eligible for the trial, patients had to be transfusion-dependent, defined as requiring at least four units of packed red blood cells over an eight-week period during the 16 weeks prior to entry into the trial.

“In the landmark IMerge randomized phase 3 trial, we showed that imetelstat, a first-in-class telomerase inhibitor, leads to durable red blood cell transfusion independence and a significant improvement in anemia in heavily transfused lower risk MDS patients across the mutational spectrum,” Zeidan added.

Approximately 68 percent of patients receiving imetelstat experienced neutropenia (low count of white blood cells) and 62 percent of patients had a low platelet count in their blood. No treatment-related deaths were reported.

“The main adverse events, namely neutropenia and thrombocytopenia, while frequent were generally reversible and tolerable,” said Zeidan, who is also interim chief of the Hematologic Malignancies division at Yale Cancer Center. “It is my hope that the IMerge study results will lead to approval of imetelstat by the regulators, and that the drug would become available in the year 2024 as an important therapeutic option for our patients.”

Submitted by Michael Masciadrelli on December 04, 2023