In the phase 3 IMerge trial, patients with lower-risk myelodysplastic syndromes (LR-MDS) who were not responding to or were ineligible for erythropoiesis-stimulating agents (ESAs) had durable transfusion independence (approximately 1 year) and disease-modifying activity during treatment with the competitive telomerase inhibitor imetelstat, researchers report.
Adult participants were recruited from 118 university hospitals, cancer centers, and outpatient clinics in 17 countries. All were heavily transfused patients with red blood cell transfusion-dependent (RBC-TD) LR-MDS; they were randomized to imetelstat 7.5 mg/kg or placebo intravenous infusions every 4 weeks until disease progression, unacceptable toxic effects, or withdrawal of consent.
Based on a primary endpoint of the 8-week RBC transfusion independence (RBC-TI) rate, the study showed the following: “Between Sept. 11, 2019, and Oct. 13, 2021, 178 patients were enrolled and randomly assigned (118 to imetelstat and 60 to placebo). 111 (62%) were male and 67 (38%) were female. 91 (77%) of 118 patients had discontinued treatment by data cutoff in the imetelstat group versus 45 (75%) in the placebo group; a further one patient in the placebo group did not receive treatment. Median follow-up was 19.5 months (IQR 12.0–23.4) in the imetelstat group and 17.5 months (12.1–22.7) in the placebo group. In the imetelstat group, 47 (40% [95% CI 30.9–49.3]) patients had an RBC-TI of at least 8 weeks versus nine (15% [7.1–26.6]) in the placebo group (rate difference 25% [9.9 to 36.9]; P = 0.0008). Overall, 107 (91%) of 118 patients receiving imetelstat and 28 (47%) of 59 patients receiving placebo had grade 3–4 treatment-emergent adverse events. The most common treatment-emergent grade 3–4 adverse events in patients taking imetelstat were neutropenia (80 [68%] patients who received imetelstat vs two [3%] who received placebo) and thrombocytopenia (73 [62%] vs five [8%]). No treatment-related deaths were reported.”