Imelelstat Approved For Lower-Risk MDS: New Hope for Transfusion-Dependent MDS Patients

On June 6, 2024, the FDA announced that it had approved imelelstat (Rytelo, Geron) for the treatment of adult patients with low to intermediate-risk myelodysplastic syndromes. This medication is designed for patients with transfusion-dependent anemia (requiring four or more red blood cell units over 8 weeks).

What Do We Know About Imetelstat?

Imetetelstat is a new type of medication called a telomerase inhibitor. It works by stopping the repair tool called telomerase, which helps MDS cells to keep dividing uncontrollably. Cancer cells can't keep dividing as quickly when the telomerase is inhibited. This can help the bone marrow produce more healthy red blood cells, reducing the need for blood transfusions.

Imetetelstat is a targeted therapy developed for a specific type of MDS – low-to-intermediate risk MDS with transfusion-dependent anemia. It's a new option for patients who haven't responded well to erythropoiesis-stimulating agents (ESA). It is administered as an intravenous infusion over 2 hours every 4 weeks.

“For patients with lower-risk MDS and anemia who are transfusion dependent, we have very few options today and often cycle through available therapies, making the approval of imetesltat potentially practice changing for us,” said Rami Komrokji, from the Moffitt Cancer Center, who was an investigator of the IMerge clinical trial. 

IMerge Phase 3 Clinical Trial Data Backs the Approval of Imetelstat

The research for imelelstat was conducted in the IMerge trial (NCT02598661), a large clinical trial with over 170 patients that investigated the effectiveness and safety of imetelstat for low-risk MDS patients who rely on regular blood transfusions. The study compared imetelstat to a placebo, with both groups receiving supportive care, including transfusions.

Results:

• Reduced transfusion dependence: Significantly more patients receiving imetelstat achieved red blood cell transfusion independence than those on placebo.
  • At 8 weeks: 39.8% with imetelstat vs 15% with placebo
  • At 24 weeks: 28% with imetelstat vs 3.3% with placebo
  • This benefit seemed to last for a significant period, with an average duration of transfusion independence exceeding 1 year for some patients
• Increased hemoglobin levels: Patients treated with imetelstat showed a noticeable increase in hemoglobin levels compared to the placebo group.
• Effective across subgroups: The positive effects of imetelstat were observed regardless of factors like ring sideroblast status, initial transfusion needs, or specific MDS risk category.

Safety Profile:

• Manageable side effects: The most common side effects observed with imetelstat were decreased levels of platelets and white blood cells, which are familiar side effects managed by hematologists. These effects were usually short-lived (lasting less than 2 weeks) and resolved quickly in most patients.
• Other side effects: Alterations of hepatic enzyme levels, fatigue, joint and muscle pain, and headaches.
• Dose adjustments: In some cases, doctors were able to adjust the dose of imetelstat to manage side effects.
• Convenient administration: Imetelstat is delivered via intravenous infusion every four weeks, aligning well with routine blood monitoring schedules for MDS patients.

Overall, the IMerge trial results demonstrate the potential of imetelstat to significantly reduce transfusion dependence and improve hemoglobin levels in patients with lower-risk MDS. The safety profile appears manageable, with side effects being short-lived and treatable.

In Conclusion

Lower-risk myelodysplastic syndromes can be a challenging condition. For some patients, the disease can slowly worsen, leading to symptoms like fatigue and an increased need for blood transfusions. These transfusions, while helpful, can have side effects and impact quality of life. The recent approval of imetelstat offers new hope for patients who rely on regular blood transfusions. This medication is designed to help the body produce more healthy red blood cells, potentially reducing the need for transfusions and improving overall well-being.

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Sources:

• 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
• 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