Updated results from the phase 3 IMerge study presented at the 2024 Society of Hematologic Oncology Annual Meeting (SOHO) demonstrate that imetelstat (Rytelo) provides sustained red blood cell transfusion independence (RBC-TI) in patients with lower-risk transfusion-dependent myelodysplastic syndrome (MDS) without negatively impacting overall survival (OS).
In the study, 83% of patients who responded to imetelstat (n = 47) achieved a single continuous RBC-TI period of at least 8 weeks. The median duration of RBC-TI was 51.6 weeks (95% CI, 26.9-80.4) in the imetelstat arm versus 13.3 weeks (95% CI, 8.0-24.9) in the placebo arm (n = 9).
Durable Responses with Imetelstat
Among patients in the imetelstat arm who achieved RBC-TI for at least 8 weeks, at least 24 weeks, and at least 1 year after treatment initiation, the median durations of RBC-TI were 52 weeks, 80 weeks, and 132 weeks, respectively. Seventy percent of patients in the imetelstat arm who achieved RBC-TI for at least 8 weeks went on to have RBC-TI for at least 24 weeks, and 64% of patients in the imetelstat arm who achieved RBC-TI for at least 24 weeks went on to have RBC-TI for at least 1 year.
According to lead study author Dr. Valeria Santini, associate professor of hematology at the University of Florence Medical School in Italy, "The data indicate clearly that the majority of patients responding to imetelstat do have a very durable response, and the clinical benefit is clear."
FDA Approval and IMerge Trial Design
On June 6, 2024, the FDA approved imetelstat for the treatment of adult patients with low- to intermediate-1–risk MDS and transfusion-dependent anemia requiring at least 4 RBC units over 8 weeks who have lost response to, not responded to, or are not eligible for erythropoiesis-stimulating agents (ESAs). This decision was based on prior findings from the IMerge trial. The primary analysis of IMerge demonstrated significantly higher rates of RBC-TI at least 8 weeks, at least 24 weeks, and at least 1 year after initiating treatment with imetelstat (n = 118) vs placebo (n = 60), at 39.8% (95% CI, 30.9%-49.3%), 28.0% (95% CI, 20.1%-26.6%), and 17.8%, respectively, vs 15.0% (95% CI, 7.1%-26.6%; P < .001), 3.3% (95% CI, 0.4%-11.5%; P < .001), and 1.7%, respectively, in the intention-to-treat (ITT) population. The most common adverse effects observed with imetelstat were thrombocytopenia and neutropenia, which were generally resolvable to grade 2 or below and were manageable with dose modifications.
The double-blind, randomized IMerge trial was conducted at 118 clinical sites across 17 countries and enrolled 178 patients with International Prognostic Scoring System (IPSS) low- or intermediate-1–risk MDS who had relapsed on or were refractory to ESAs. Patients were randomly assigned 1:1 to receive either imetelstat at 7.1 mg/kg every 4 weeks or placebo. The trial’s primary end point was RBC-TI at least 8 weeks from the start of study treatment. Key secondary end points included RBC-TI at least 24 weeks, duration of RBC-TI, and hematologic improvement–erythroid.
Hemoglobin Normalization and Survival Outcomes
The rates of patients who achieved RBC-TI with a concurrent hemoglobin increase of at least 1.5 g/dL were higher among patients in the imetelstat arm vs the placebo arm. Treatment with imetelstat did not lead to an OS detriment vs placebo in the ITT population. At respective median durations of follow-up of 32 months and 28 months, the median OS was 40.4 months with imetelstat vs not evaluable (NE) with placebo (HR, 0.98; 95% CI, 0.53-1.82).
"More studies will be needed to clarify the mechanism of action [of imetelstat] and the possibility to obtain longer response," Santini concluded.
