Dr Sekeres on the FDA Approval of Imetelstat in Lower-Risk MDS With Anemia

Mikkael A. Sekeres, MD, professor, medicine, chief, Division of Hematology, Leukemia Section, the University of Miami Sylvester Comprehensive Cancer Center, discusses the significance of the FDA approval of imetelstat (Rytelo) for patients with lower-risk myelodysplastic syndromes (MDS) and transfusion-dependent anemia.

On June 6, 2024, the FDA approved imetelstat for the treatment of adult patients with low-to-intermediate-1–risk MDS and anemia requiring at least 4 red blood cell (RBC) units over 8 weeks who have lost response to, not responded to, or are not eligible for erythropoiesis-stimulating agents (ESAs). This regulatory decision was supported by data from the phase 2/3 IMerge trial (NCT02598661), which demonstrated that 39.8% (95% CI, 30.9%-49.3%) of patients in the imetelstat arm (n = 118) achieved RBC transfusion independence at week 8 vs 15% (95% CI, 7.1%-26.6%) of those in the placebo arm (n = 59; P < .001).

The FDA approval of imetelstat for patients with transfusion-dependent, lower-risk MDS expands the already-sparse treatment paradigm for this patient population, Sekeres says. Patients with lower-risk MDS with anemia typically receive ESAs, followed by lenalidomide (Revlimid) in those with deletion 5q gene mutations, Sekeres explains.

Furthermore, in 2023, luspatercept-aamt (Reblozyl) received FDA approval for the frontline treatment of anemia in adult patients with lower-risk MDS who may require regular RBC transfusions and have not received prior ESAs. Luspatercept was previouslyapproved by the FDA in 2020 for the treatment of anemia in adult patients with lower-risk MDS with ring sideroblasts who progressed on an ESA and require at least 2 RBC units over 8 weeks. However, luspatercept is most effective in patients with either a spliceosome mutation or ring sideroblasts, Sekeres emphasizes. For patients who do not have spliceosome mutations, ring sideroblasts, or deletion 5q gene mutations, the standard of care has been HMAs. Imetelstat expands the treatment arsenal for these patients, and can be given before or after HMA exposure, Sekeres concludes.