Imetelstat Hits Transfusion Independence Goal in Low-Risk Myelodysplastic Syndrome

Imetelstat improves eight- and 24-week transfusion independence in patients with low-risk myelodysplastic syndrome, according to topline study results.

The phase 3 IMerge trial met its main goal, showing that patients treated with imetelstat had improved eight-week transfusion independence (did not require a red blood cell or platelet transfusion) compared to placebo in patients with relapsed or refractory myelodysplastic syndrome (MDS). All patients had disease that is not eligible for treatment with erythropoiesis stimulating agents (ESAs), according to Geron, the manufacturer of the agent.

MDS is a blood cancer that can cause low platelet and red blood cell counts, causing patients to rely on transfusions.

“The IMerge phase 3 efficacy results illustrate the depth, breadth and durability of transfusion independence potentially achievable with imetelstat treatment — which could be practice changing if approved,” said Dr. Uwe Platzbecker, a principal investigator of the trial, in a press release. “These results are especially encouraging, because today we have limited treatment options for lower-risk MDS patients that provide broad and durable transfusion independence.”

Topline data from the IMerge trial — which included patients with low-risk, transfusion-dependent MDS — showed that 39.8% of patients given imetelstat did not need to undergo a transfusion for at least eight weeks. Only 9% of patients given a placebo achieve an eight-week transfusion independence.

“Today is a great day for lower risk MDS patients who are living with the burden of transfusions. The results from the IMerge Phase 3 study were resoundingly positive, presenting compelling durability of transfusion independence, delivering on the promise of imetelstat and telomerase inhibition for these patients,” said Dr. John A. Scarlett, Geron’s chairman and chief executive officer, in the release.

Further, the trial achieved its secondary goal of improved 24-week transfusion independence, with 28% and 2% achieving this milestone in the imetelstat and placebo groups, respectively.

The imetelstat group had a higher rate of hematologic improvement-erythroid, which shows improvement in transfusion-independent erythroid cell levels for 16 weeks, at 42.4% compared to 13.3% for the placebo group.

“(Imetelstat) has the potential to become a first-in-class therapy for lower-risk MDS patients. The meaningful clinical results observed in the trial, including duration of (transfusion independence), increases in hemoglobin levels, decreases in transfusions and reductions in mutation burdens, suggest imetelstat treatment may be altering the course of the disease,” said Dr. Faye Feller, chief medical officer of Geron, in the release.

A total of 77.1% and 76.3% of patients in the imetelstat and placebo groups discontinued treatment — 23.7% of patients stopped treatment with imetelstat due to lack of efficacy, compared to 42.4% in the placebo group. No patients discontinued placebo due to side effects, whereas 16.1% did in the imtelstat group.

Side effects from imetelstat in the IMerge trial were consistent with side effects previously observed in other trials of the drug.

The most common non-blood-related side effects seen with imetelstat were weakness/lack of energy, COVID-19, leg swelling, headache, diarrhea and alanine aminotransferase increase, which could be a sign of liver disease.

Common blood-related side effects were moderate to severe thrombocytopenia (61.9% in the imetelstat group, compared to 8.5% in the placebo group) and neutropenia (67.8% versus 3.4%), and tended to last a shorter duration in patients given imetelstat.

Thrombocytopenia and neutropenia — both decreases in specific types of white blood cells — can cause other complications, such as bleeding events, infections and febrile neutropenia. Moderate (grade 3) rates of these events were similar between the two groups.

“With regards to the safety results, cytopenias were manageable and reversible. Importantly for hematologists, who are accustomed to managing cytopenias, clinical consequences were limited and similar to placebo-treated patients. As a once per month out-patient (intravenous) therapy, imetelstat will hopefully become a novel treatment option for lower risk MDS patients in the near future,” Platzbecker said.

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