FDA Oks Imetelstat in Lower-Risk MDS With Transfusion-Dependent Anemia


The FDA approved imetelstat for treating patients with lower-risk myelodysplastic syndromes with transfusion-dependent anemia, regardless of ring sideroblast status.

  • Imetelstat showed effectiveness in the IMerge/MDS3001 trial (NCT02598661).
  • A significantly higher percentage of patients achieved transfusion independence for at least 8 weeks in the imetelstat arm compared with placebo.
  • This approval is intended for treatment of adult patients with low- to intermediate-1 risk myelodysplastic syndromes (MDS) with transfusion-dependent anemia that requires at least 4 red blood cell units over 8 weeks who have not responded to, or have lost response to, or are ineligible for erythropoiesis-stimulating agents (ESAs).

The FDA has approved imetelstat for the treatment of patients with transfusion-dependent anemia and lower-risk MDS who are ineligible for ESAs.1

Results from the IMerge/MDS3001 study support this regulatory decision as the study met its primary end point. In the experimental imetelstat arm, 40% of patients (n = 40) achieved red blood cell (RBC) transfusion independence (RBC-TI) of at least 8 weeks (95% CI 30.9–49.3) compared with 15% of patients (n = 9) in the placebo arm (95% CI, 7.1–26.6; P <.001).2 RBC-TI rates for at least 24 weeks were 28.0% (95% CI 20.1-37.0) vs 3.3% (95% CI 0.4-11.5), respectively (P <.001).

Safety findings showed that 91% of patients who received imetelstat and 47% of those given placebo had grade 3 to 4 treatment-emergent adverse events. These included neutropenia (68% vs 3%) and thrombocytopenia (62% vs 8%). No treatment-related deaths were reported.

However, these safety issues were quickly resolved, according to Amer Zeidan, MBBS, associate professor at Yale School of Medicine.

“In my view, the data [are] favorable in terms of getting the drug approved. My sense is that imetelstat, once it is used in the community, people have to pay attention to the blood counts, because as I mentioned, it does cause neutropenia and thrombocytopenia. Some patients might need growth factors or transfusions, but generally it is manageable,” explained Zeidan in an interview with Targeted OncologyTM.

Amer Zeidan, MBBS

Amer Zeidan, MBBS

About the IMerge/MDS3001 Trial of Imetelstat

Imetelstat is a liquidated oligonucleotide and a telomerase inhibitor. In March 2024, the FDA’s Oncologic Drug Advisory Committee voted that the benefits of imetelstat outweigh the risks for patients with lower-risk MDS with anemia who are transfusion-dependent and ineligible for ESAs.3

In the phase 2/3 randomized, multicenter trial, patients aged 18 years and older with MDS and an ECOG performance status of 0, 1, or 2, were randomly assigned to 1 of 2 arms: Two-thirds of the patients received imetelstat while the other third received a placebo.2

The primary end point for parts 1 and 2 of the trial were to evaluate the percentage of patients without any RBC transfusion during any consecutive 8-week period. Secondary end points included assessing adverse events, duration of RBC transfusion independence (TI), time to 8-week RBC TI, percentage of patients with hematologic improvement, percentage of patients with complete or partial remission, overall survival, progression-free survival, time to progression to acute myeloid leukemia, amount of RBC transfusions, relative change in RBC transfusions, percentage of patients receiving any myeloid growth factors, and pharmacokinetics.

Findings were published in The Lancet in December 2023.

1. Geron Announces FDA Approval of RYTELO™ (imetelstat), a First-in-Class Telomerase Inhibitor, for the Treatment of Adult Patients with Lower-Risk MDS with Transfusion-Dependent Anemia. Geron Corporation. News release. June 6, 2024. Accessed June 6, 2024. https://www.businesswire.com/news/home/20240606850162/en/Geron-Announces-FDA-Approval-of-RYTELO%E2%84%A2-imetelstat-a-First-in-Class-Telomerase-Inhibitor-for-the-Treatment-of-Adult-Patients-with-Lower-Risk-MDS-with-Transfusion-Dependent-Anemia
2. Platzbecker U, Santini V, Fenaux P, et al. Imetelstat in patients with lower-risk myelodysplastic syndromes who have relapsed or are refractory to erythropoiesis-stimulating agents (IMerge): a multinational, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2024;403(10423)P249-260. doi:10.1016/S0140-6736(23)01724-5
3. Oncologic Drugs Advisory Committee (ODAC) Meeting. FDA. March 14, 2024. Accessed March 14, 2024.
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