As reported in The Lancet by Uwe Platzbecker, MD, and colleagues, the phase III IMerge trial has shown improved red blood cell transfusion independence with imetelstat, a competitive telomerase inhibitor, vs placebo in RBC transfusion-dependent patients with lower-risk myelodysplastic syndromes who did not respond to or were ineligible for erythropoiesis-stimulating agents.
Uwe Platzbecker, MD
In the double-blind trial, 178 patients from sites in 17 countries were randomly assigned 2:1 between September 2019 and October 2021 to receive imetelstat at 7.5 mg/kg (n = 118) or placebo (n = 60) every 4 weeks until disease progression or unacceptable toxicity. The primary endpoint was 8-week RBC transfusion independence in the intent-to-treat population.
RBC Transfusion Independence
Median follow-up was 19.5 months (interquartile range = 12.0–23.4 months) in the imetelstat group and 17.5 months (IQR = 12.1–22.7) in the placebo group. RBC transfusion independence for ≥ 8 weeks was observed in 47 patients (40%, 95% confidence interval [CI] = 30.9%–49.3%) in the imetelstat group vs 9 patients (15%, 95% CI = 7.1%–26.6%) in the placebo group (rate difference = 25%, 95% CI = 9.9%–36.9%, P = .0008).
Continuous RBC transfusion independence for ≥ 24 weeks was observed in 33 patients (28%, 95% CI = 20.1%–37.0%) in the imetelstat group vs 2 patients (3%, 95% CI = 0.4%–11.5%) in the placebo group (rate difference = 25%, 95% CI = 12.6%–34.2%, P = .0001).
Among patients with RBC transfusion independence for ≥ 8 weeks, median duration of RBC transfusion independence was 51.6 weeks (95% CI = 26.9–83.9 weeks) in the imetelstat group vs 13.3 weeks (95% CI = 8.0–24.9 weeks) in the placebo group (hazard ratio = 0.23, 95% CI = 0.09–0.57).
KEY POINTS
- Imetelstat was associated with a higher rate of 8-week RBC transfusion independence vs placebo.
- Among patients with RBC transfusion independence for ≥ 8 weeks, median RBC transfusion independence was 51.6 vs 13.3 weeks.
Adverse Events
Grade 3 or 4 adverse events occurred in 91% of patients in the imetelstat group vs 47% of the placebo group. The most common in the imetelstat group were neutropenia (68%), thrombocytopenia (62%), and anemia (19%); the most common in the placebo group were thrombocytopenia (8%) and anemia (7%). Serious adverse events occurred in 32% vs 22% of patients. Adverse events leading to discontinuation of imetelstat included neutropenia (5%) and thrombocytopenia (3%). No treatment-related deaths were reported.
The investigators concluded, “Imetelstat offers a novel mechanism of action with durable transfusion independence (approximately 1 year) and disease-modifying activity for heavily transfused patients with lower-risk myelodysplastic syndromes who are not responding to or are ineligible for erythropoiesis-stimulating agents.”
Uwe Platzbecker, MD, of the Department of Hematology, Cellular Therapy, Infectious Diseases, and Hemostaseology, University Hospital Leipzig, is the corresponding author for The Lancet article.
Disclosure: The study was funded by Janssen Research & Development before April 18, 2019, and Geron Corporation thereafter. For full disclosures of the study authors, visit thelancet.com.
