Imetelstat Sodium (Monograph)

Brand name: Rytelo
Drug class: Antineoplastic Agents

Medically reviewed by Drugs.com on Aug 10, 2024. Written by ASHP.

Introduction

Imetelstat sodium is an oligonucleotide telomerase inhibitor.

Uses for Imetelstat Sodium

Imetelstat sodium has the following uses:

Imetelstat sodium is indicated for the treatment of adult patients with low- to intermediate-1 risk myelodysplastic syndromes (MDS) with transfusion-dependent anemia requiring 4 or more red blood cell units over 8 weeks who have not responded to or have lost response to or are ineligible for erythropoiesis-stimulating agents (ESA).

Imetelstat Sodium Dosage and Administration

General

Imetelstat sodium is available in the following dosage form(s) and strength(s):

Single-dose vial containing 47 mg of imetelstat lyophilized powder for reconstitution and dilution.
Single-dose vial containing 188 mg of imetelstat lyophilized powder for reconstitution and dilution.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

The recommended dosage of imetelstat is 7.1 mg/kg administered as an IV infusion over 2 hours every 4 weeks. Discontinue treatment if a patient does not experience a decrease in red blood cell (RBC) transfusion burden after 24 weeks of treatment (administration of 6 doses) or if unacceptable toxicity occurs at any time.
Premedicate with diphenhydramine and hydrocortisone at least 30 minutes prior to dosing to prevent or reduce potential infusion-related reactions.
Monitor patients for adverse reactions for at least 1 hour after the infusion has been completed.
See full prescribing information for preparation and administration instructions and also for dosage modification recommendations for adverse reactions.

Cautions for Imetelstat Sodium

Contraindications

None.

Warnings/Precautions

Thrombocytopenia

Imetelstat can cause thrombocytopenia based on laboratory values. In the principal clinical trial, new or worsening Grade 3 or 4 decreased platelets occurred in 65% of patients with MDS treated with imetelstat.

Median time to onset of first occurrence of Grade 3 or 4 decreased platelets was 6 weeks (range: 2 to 88 weeks) and median time to recovery from each occurrence of Grade 3 or 4 decreased platelets to Grade 2 or lower, or last value available, was 1.3 weeks (range: 0.1 to 13 weeks). Grade 3 or 4 decreased platelets occurred throughout treatment with imetelstat, with 48% of patients experiencing Grade 3 or Grade 4 thrombocytopenia during cycles 1-3, 31% during cycles 4-6, 33% during cycles 7-12, and 24% during cycles 13 and beyond. Grade 3 or 4 bleeding was seen in 2.5% of patients, including GI bleeding (1.7%) and hematuria (0.8%).

Monitor patients with thrombocytopenia for bleeding.

Monitor complete blood cell counts prior to initiation of imetelstat, weekly for the first two cycles, prior to each cycle thereafter, and as clinically indicated. Administer platelet transfusions as appropriate. Delay the next cycle and resume at the same or reduced dose, or discontinue as recommended.

Neutropenia

Imetelstat can cause neutropenia based on laboratory values. In the principal clinical trial, new or worsening Grade 3 or 4 decreased neutrophils occurred in 72% of patients with MDS treated with imetelstat.

Median time to onset of first occurrence of Grade 3 or 4 decreased neutrophils was 4.6 weeks (range: 1 to 81 weeks) and median time to recovery from each occurrence of Grade 3 or 4 decreased neutrophils to Grade 2 or lower, or last value available, was 1.9 weeks (range: 0 to 16 weeks). Grade 3 or 4 decreased neutrophils occurred throughout treatment with imetelstat, with 65% of patients experiencing Grade 3 or Grade 4 neutropenia during cycles 1-3, 35% during cycles 4-6, 32% during cycles 7-12, and 39% during cycles 13 and beyond. Febrile neutropenia occurred in 0.8% and sepsis in 4.2%.

Monitor patients with Grade 3 or 4 neutropenia for infections, including sepsis.

Monitor complete blood cell counts prior to initiation of imetelstat, weekly for the first two cycles, prior to each cycle thereafter, and as clinically indicated. Administer growth factors and anti-infective therapies for treatment or prophylaxis as appropriate. Delay the next cycle and resume at the same or reduced dose, or discontinue as recommended.

Infusion-related Reactions

Imetelstat can cause infusion-related reactions. In the principal clinical trial, infusion-related reactions occurred in 8% of patients with MDS treated with imetelstat; Grade 3 or 4 infusion-related reactions occurred in 1.7%, including hypertensive crisis (0.8%). The most common infusion-related reaction was headache (4.2%). Infusion-related reactions usually occur during or shortly after the end of the infusion.

Premedicate patients at least 30 minutes prior to infusion with diphenhydramine and hydrocortisone as recommended and monitor patients for at least one hour following the infusion as recommended. Manage symptoms of infusion-related reactions with supportive care and infusion interruptions, decrease infusion rate, or permanently discontinue as recommended.

Embryo-fetal Toxicity

Based on findings in animals, imetelstat can cause embryo-fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of imetelstat to pregnant mice during the period of organogenesis resulted in embryo-fetal mortality at maternal exposures (AUC) 2.5-times the human exposure at the recommended clinical dose. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with imetelstat and for 1 week after the last dose.

Specific Populations

Pregnancy

Based on findings in animal studies, imetelstat can cause embryo-fetal harm when administered to a pregnant woman. There are no available data on imetelstat use in pregnant women to evaluate for drug-associated risk. In embryo-fetal developmental toxicity studies, administration of imetelstat to pregnant mice and rabbits during the period of organogenesis resulted in embryo-fetal mortality, which in mice occurred at maternal exposures approximately 2.5 times the human exposure at the recommended clinical dose. Advise pregnant women of the potential risk to a fetus.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Lactation

There is no data on the presence of imetelstat in human milk, or the effects imetelstat on the breastfed child, or milk production. Because of the potential for adverse reactions in breastfed children, advise women not to breastfeed during treatment with imetelstat and for 1 week after the last dose.

Females and Males of Reproductive Potential

Based on findings from animal studies, imetelstat can cause embryo-fetal harm when administered to a pregnant woman.

Verify the pregnancy status of females of reproductive potential prior to initiating treatment with imetelstat.

Advise females of reproductive potential to use effective contraception during treatment with imetelstat and for 1 week after the last dose.

Based on findings in animals, imetelstat may impair fertility in females of reproductive potential. The effect on fertility is reversible.

Pediatric Use

Safety and effectiveness of imetelstat in pediatric patients have not been established.

Geriatric Use

Of the 118 patients with low- to intermediate-1 risk myelodysplastic syndromes (MDS) in the principal clinical trial who received imetelstat, 91 (77.1%) patients were 65 years of age and older and 35 (29.7%) patients 75 years of age and older. No differences in safety or efficacy were observed between older (≥ 65 years) and younger patients.

Common Adverse Effects

Most common adverse reactions (incidence ≥10% with a difference between arms of >5% compared to placebo), including laboratory abnormalities, are decreased platelets, decreased white blood cells, decreased neutrophils, increased AST, increased alkaline phosphatase, increased ALT, fatigue, prolonged partial thromboplastin time, arthralgia/myalgia, COVID-19 infections, and headache.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Actions

Mechanism of Action

Imetelstat is an oligonucleotide human telomerase inhibitor that binds to the template region of the RNA component of human telomerase (hTR), inhibits telomerase enzymatic activity and prevents telomere binding.

Increased telomerase activity and human telomerase reverse transcriptase (hTERT) RNA expression have been reported in MDS and malignant stem and progenitor cells. Nonclinical studies showed imetelstat treatment led to reduction of telomere length, reduction of malignant stem and progenitor cell proliferation, and induction of apoptotic cell death.

Advice to Patients

Advise the patient to read the FDA-approved patient labeling (Medication Guide).
Advise patients of the risk of thrombocytopenia with imetelstat, and that their blood counts will be monitored routinely while on treatment and dose of imetelstat delayed or reduced as needed. Instruct patients to notify a healthcare provider immediately if they show signs or symptoms of thrombocytopenia such as unusual bleeding or bruising.
Advise patients of the risk of neutropenia with imetelstat and that their blood counts will be monitored routinely while on treatment and dose of imetelstat delayed or reduced as needed. Instruct patients to notify a healthcare provider immediately if they show signs or symptoms of neutropenia, such as fever or infection.
Inform patients that infusion-related reactions can occur during treatment with imetelstat and premedications will be given prior to each infusion. Patients will be monitored by their healthcare provider for at least an hour after the infusion. Advise patients that their healthcare provider may decide to give imetelstat more slowly or stop the infusion if an infusion-related reaction occurs.
Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to inform their healthcare provider if they are pregnant or become pregnant.
Advise women not to breastfeed during treatment with imetelstat and for 1 week after the last dose.

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.