IMerge Trial
Panelists discuss findings from the IMerge phase 3 trial of imetelstat in lower-risk myelodysplastic syndromes, emphasizing its impact on transfusion independence and fatigue improvement, and advocating for a sequential, patient-centered treatment approach to enhance quality of life and long-term outcomes.
EP: 1.Early vs Late Onset of ESA in LR-MDS: Results From Phase 3 EPO-PRETAR Trial
EP: 2.COMMANDS and ELEMENT-MDS Trials: Long-Term Analysis, Survival, Duration of Response, and Hemoglobin Levels
EP: 3.IMerge Trial
EP: 4.Debate: Optimal Initiation of ESAs, Luspatercept, and Imetelstat: Pretransfusion vs Posttransfusion
The IMerge phase 3 trial evaluated imetelstat, a first-in-class telomerase inhibitor, in patients with lower-risk myelodysplastic syndromes (MDS) who were relapsed, refractory to, or ineligible for erythropoiesis-stimulating agents (ESAs). The study enrolled 178 patients, all of whom were non-del(5q), had no prior exposure to lenalidomide or hypomethylating agents, and had serum erythropoietin levels of at least 500 mU/mL. Participants were red blood cell (RBC) transfusion dependent, receiving at least 4 units over 8 weeks. Patients were randomly assigned 2:1 to imetelstat or placebo. The primary end point was 8-week RBC transfusion independence (RBC-TI), with key secondary end points including 24-week RBC-TI, hematologic improvement, safety, and patient-reported outcomes (PROs).
PROs data, presented at the American Society of Hematology Annual Meeting and Exposition, showed notable improvements in fatigue among patients receiving imetelstat, especially those with higher transfusion burdens or hemoglobin increases of 1.5 g/dL or greater. For example, patients with baseline transfusion burdens of 6-plus units over 8 weeks reported a 57% rate of meaningful fatigue improvement with imetelstat, compared with 46% with placebo. Among those with significant hemoglobin improvements, 70% reported improved fatigue in the imetelstat group vs 40% in placebo. These results suggest that clinical response—particularly reductions in transfusion need and rises in hemoglobin—closely correlates with improved symptoms and quality of life.
While the trial was not designed to assess survival outcomes, the data highlight the broader impact of treatment beyond hematologic metrics. Importantly, placebo-treated patients showed a decline in quality of life over time, underscoring the burden of transfusion dependence. Imetelstat’s role may therefore be best understood within a treatment sequence rather than in isolation—especially when considered alongside other agents like luspatercept. Rather than positioning therapies in competition, these data support a model of sequential, individualized treatment to optimize long-term outcomes and patient well-being in lower-risk MDS.
