Imetelstat (Rytelo) Treatment Effects

On June 6, 2024, the U.S. Food and Drug Administration approved imetelstat (Rytelo, Geron Corporation), an oligonucleotide telomerase inhibitor, for adult patients with low- to intermediate-1 risk myelodysplastic syndrome (MDS) and transfusion-dependent anemia who require four or more red blood cell therapies. Blood cell units that are unresponsive or have lost response to erythropoiesis stimulating agents (ESA) for more than 8 weeks or are not suitable for use with erythropoiesis stimulating agents (ESA).

Efficacy was evaluated in IMerge (NCT02598661), a randomized (2:1), double-blind, placebo-controlled multicenter trial in 178 patients with MDS. Patients received intravenous infusions of imetelstat 7.1 mg/kg or placebo during 28-day treatment cycles until disease progression or unacceptable toxicity. Randomization was stratified by previous red blood cell (RBC) transfusion burden and International Prognostic Scoring System (IPSS) risk group. All patients received supportive care, including red blood cell transfusions.

Efficacy was determined based on the proportion of patients achieving ≥8 weeks, after a median follow-up of 19.5 months (range: 1.4 to 36.2) in the imetelstat group and 17.5 months (range: 0.7 to 34.3) in the placebo group. ≥24 weeks red blood cell transfusion independence (RBC-TI), defined as the absence of red blood cell transfusion therapy, if any, during any consecutive 8-week period and any consecutive 24-week period, respectively, from randomization to the start of subsequent anticancer therapy. The incidence of RBC-TI at ≥8 weeks was 39.8% (95% CI: 30.9, 49.3) in the imetelstat group and 15% (95% CI: 7.1, 26.6) in the placebo group (p value < 0.001). The incidence of RBC-TI at ≥24 weeks was 28% (95% CI: 20.1, 37) in the imetelstat group and 3.3% (95% CI: 0.4, 11.5) in the placebo group (p value < 0.001).

The most common adverse reactions (incidence≥10% compared to placebo, >5% difference between groups) include laboratory abnormalities including thrombocytopenia, leukopenia, neutropenia, increased aspartate aminotransferase, increased alkaline phosphatase, increased alanine aminotransferase, fatigue, prolonged partial thromboplastin time, arthralgia/myalgia, COVID-19 infection, and headache.

The recommended imetelstat dose is 7.1 mg/kg as an intravenous infusion over 2 hours every 4 weeks.

In conclusion,Imetelstat (Rytelo) demonstrated significant and durable efficacy in the treatment of adult patients with low- to intermediate-1 risk myelodysplastic syndrome (MDS) and transfusion-dependent anemia, with a favorable safety profile.