Imetelstat Approved for Low- to Intermediate-1–Risk Myelodysplastic Syndromes

The FDA has granted approval to imetelstat (Rytelo™, Geron Corporation), an oligonucleotide telomerase inhibitor, for adults with low- to intermediate-1–risk myelodysplastic syndromes (MDS) with transfusion-dependent anemia requiring four or more red blood cell (RBC) units over eight weeks, who have not responded to, have lost response to, or are ineligible for erythropoiesis-stimulating agents (ESAs).

Why it matters: “Unmet medical needs remain in patients with red blood cell transfusion–dependent (RBC-TD) lower-risk myelodysplastic syndromes (LR-MDS) who are not responding to or are ineligible for ESAs,” wrote Uwe Platzbecker, MD, Director of the Clinic and Polyclinic for Hematology, Cell Therapy, and Hemostaseology at the Leipzig University Hospital in Leipzig, Germany, and colleagues, in their published results of the IMerge trial (NCT02598661), on which approval was based. “Imetelstat, a competitive telomerase inhibitor, showed promising results in a phase 2 trial.”

What they studied: Efficacy was studied in the phase 2/3, double-blind, placebo-controlled, multicenter trial in which 178 MDS patients were enrolled. Patients were randomized 2:1 to receive either a 7.1 mg/kg intravenous infusion of imetelstat or placebo in 28-day treatment cycles, until disease progression or unacceptable toxicity. Enrolled patients were randomized based on prior RBC transfusion burden and by International Prognostic Scoring System (IPSS) risk group. All patients received supportive care, which included RBC transfusions.

The primary efficacy outcome measured was ≥8-week and ≥24-week RBC transfusion independence (RBC-TI), as defined by the absence of RBC transfusion during any consecutive 8-week or 24-week period, respectively, between randomization and the start of subsequent anticancer therapy.

What they found: After a median follow-up of 19.5 months in the imetelstat group and a median follow-up of 17.5 months in the placebo-controlled group, RBC-TI efficacy was established. The imetelstat group experienced an ≥8-week RBC-TI rate of 39.8% compared with the placebo-controlled group at a rate of 15%. The rate seen for ≥24-week RBC-TI was 28% in the imetelstat group compared with 3.3% in the placebo-controlled group.

Adverse events: The most common adverse events experienced by ≥10% of those receiving imetelstat, with a difference between arms of >5% compared to placebo, including laboratory abnormalities, were decreased platelets, decreased white blood cells, decreased neutrophils, increased aspartate aminotransferase, increased alkaline phosphatase, increased alanine aminotransferase, fatigue, prolonged partial thromboplastin time, arthralgia/myalgia, COVID-19 infections, and headache.

Conclusion: “Imetelstat offers a novel mechanism of action with durable transfusion independence—approximately one year—and disease-modifying activity for heavily transfused patients with lower-risk MDS who are not responding to or are ineligible for ESAs,” concluded Dr. Platzbecker and colleagues.

Instructions: The recommended dosage is 7.1 mg/kg of imetelstat administered as an intravenous infusion over two hours every four weeks.

For More Information

Platzbecker U, Santini V, Fenaux P, et al (2024). 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. Lancet, 403(10423):249-260. DOI:10.1016/S0140-6736(23)01724-5

Rytelo™ (imetelstat) prescribing information (2024). Geron Corporation. Available at: (2024). Study to evaluate imetelstat (GRN163L) in subjects with International Prognostic Scoring System (IPSS) low- or intermediate-1 risk myelodysplastic syndrome (MDS). NLM identifier: NCT02598661.

US Food and Drug Administration (2024). FDA approves imetelstat for low- to intermediate-1 risk myelodysplastic syndromes with transfusion-dependent anemia. Available at:

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