Abstract
In IMerge (NCT02598661), imetelstat resulted in significantly higher ≥8-week, ≥24-week, and ≥1-year RBC-TI rates than placebo in patients with non-del(5q) LR-MDS who were RBC-TD, relapsed/refractory (R/R) to or ineligible for erythropoiesis-stimulating agents (ESA), and lenalidomide/hypomethylating agent-naive.
Assess OS and clinical benefit of durable RBC-TI with imetelstat.
Randomized (2:1), double-blind, placebo-controlled, phase 3 trial.
Total of 118 global sites; 2019-2022.
Consenting patients with non-del(5q) LR-MDS, were RBC-TD, R/R/ineligible for ESAs, and lenalidomide/hypomethylating agent-naive.
Intravenous imetelstat 7.5 mg/kg or placebo q4wk until disease progression, unacceptable toxicity, or withdrawal of consent.
RBC-TI duration and OS calculated by Kaplan-Meier method and compared by stratified log-rank test. Cutoff dates: 10/2022 (primary analysis), 10/2023 (≥1-year RBC-TI), and 1/2024 (OS).
Among imetelstat-treated ≥8-week RBC-TI responders, median RBC-TI duration was 52 weeks (47/118 patients) versus 13 weeks with placebo (9/60 patients; P<.001); median increase from baseline in central hemoglobin was 3.6 g/dL versus 0.8 g/dL. Of imetelstat-treated ≥8-week responders, 70% remained RBC-TI for ≥24 weeks; 64% of these ≥24-week responders remained RBC-TI for ≥1 year. Among ≥24-week RBC-TI responders, median RBC-TI duration was 80 weeks with imetelstat (n=33) versus not estimable (NE) with placebo (n=2; P<.001); median hemoglobin increase was 4.2 g/dL versus 1.1 g/dL. In ≥1-year RBC-TI responders, median RBC-TI duration was 132 weeks with imetelstat (n=21) versus 131 weeks with placebo (n=1); median hemoglobin increase was 5.2 g/dL versus 1.7 g/dL. Assessed separately, ≥8-week, ≥24-week, and ≥1-year RBC-TI with concurrent hemoglobin rise of ≥1.5 g/dL occurred in 28% versus 2%, 23% versus 0%, and 17% versus 0% of patients receiving imetelstat and placebo, respectively (all P<.001). As of January 2024, median follow-up was 32 and 28 months for imetelstat (n=55/118) and placebo (n=26/60), with median OS of 40.4 months and NE, respectively (hazard ratio, 0.98; 95% CI, 0.526-1.823). For imetelstat, the 2-year OS rate was 78% overall and 81% in ≥8-week RBC-TI responders; for placebo, it was 74%.
Updated analyses confirm RBC-TI achievement with imetelstat is durable and associated with improved hemoglobin level. Preliminary OS analysis suggests no detriment with imetelstat versus placebo.
Geron Corporation.