How it is administered

Imetelstat is given as an intravenous (IV) infusion. It is supplied as a sterile, preservative-free, lyophilized powder that is reconstituted and diluted before administration. The recommended dose is 7.1 mg/kg, infused over 2 hours every 4 weeks. Premedication with diphenhydramine and hydrocortisone is recommended to reduce the risk of infusion-related reactions. The medication is only administered by healthcare professionals in a clinical setting.

How it works

Imetelstat is a telomerase inhibitor. It works by binding to the template region of the RNA component of human telomerase (hTR), which blocks the enzyme's activity and prevents telomere binding. Telomerase is an enzyme that is often more active in cancer cells, including those in myelodysplastic syndromes (MDS), helping them to survive and multiply. By inhibiting telomerase, imetelstat can reduce the length of telomeres in cancer cells, limit their ability to divide, and promote their death.

In nonclinical studies, imetelstat has been shown to reduce the proliferation of malignant stem and progenitor cells and induce apoptosis (cell death) in these cells. This mechanism is particularly relevant in MDS, where abnormal blood-forming cells can become dependent on telomerase activity for continued growth.

Who Should take it

Imetelstat is indicated for adult patients with low- to intermediate-1 risk myelodysplastic syndromes (MDS) who have transfusion-dependent anemia. Specifically, it is for those who require 4 or more units of red blood cells over 8 weeks and have not responded to, have lost response to, or are ineligible for erythropoiesis-stimulating agents (ESA).

This medication is intended for patients who continue to need blood transfusions despite other treatments and who do not have certain genetic abnormalities (such as del(5q)) or prior treatment with specific other drugs (like lenalidomide or hypomethylating agents). It is not used for higher-risk MDS or other types of blood cancers.

Who should not take it

There are no absolute contraindications listed for imetelstat. However, it is not recommended for use in pregnant women due to the risk of embryo-fetal harm, as shown in animal studies. Women of reproductive potential should use effective contraception during treatment and for at least one week after the last dose.

Imetelstat has not been studied in pediatric patients, and its safety and effectiveness in children are unknown. Caution is advised in patients with severe renal or hepatic impairment, as its effects in these populations have not been established.

Commonly used with

Imetelstat is typically used as a single agent in the treatment of transfusion-dependent anemia in MDS. All patients in clinical studies received supportive care, including red blood cell transfusions as needed. It is not commonly combined with other chemotherapy or disease-modifying agents for MDS.

Premedications such as diphenhydramine and hydrocortisone are given before each infusion to reduce the risk of infusion-related reactions.

Commonly tested with

In clinical trials, imetelstat was compared to placebo, with all patients receiving standard supportive care, including red blood cell transfusions. It has not been routinely tested in combination with other disease-modifying therapies for MDS, such as hypomethylating agents or lenalidomide, in the major studies leading to its approval.

Future studies may explore combinations, but current data focus on imetelstat as a single agent for this specific patient population.