Imetelstat sodium is an oligonucleotide human telomerase inhibitor.1
Imetelstat is used for the management of low- to intermediate-1 risk myelodysplastic syndromes (MDS) in adults with transfusion-dependent anemia requiring ≥4 red blood cell units over 8 weeks who have not responded to, have lost response to, or are ineligible for erythropoiesis-stimulating agents (ESA).1
Imetelstat has been designated an orphan drug by FDA for use in this indication.2
The efficacy of imetelstat was evaluated in a multinational, randomized, double-blind, placebo-controlled, phase 3 trial (IMerge) in patients with low- or intermediate-1 risk MDS who failed to respond to ESAs (ESA-refractory), lost response to ESAs (ESA-relapsed), or were ESA-ineligible.1, 3 Patients were eligible for inclusion if they were ≥18 years of age and had a bone marrow biopsy-confirmed diagnosis of International Prognostic Scoring System (IPSS) low- or intermediate-1 risk MDS, were ESA-relapsed, ESA-refractory, or ESA-ineligible (due to endogenous erythropoietin concentration >500 mU/mL) and were transfusion-dependent (i.e., requiring ≥4 units of red blood cells [RBCs] over an 8-week period within 16 weeks prior to randomization); patients were also required to have an absolute neutrophil count (ANC) of ≥1.5 x 109/L and a platelet count of ≥75 x 109/L.1 Patients were excluded if they had del(5q) MDS or were previously treated with lenalidomide or a hypomethylating agent.1, 3
A total of 178 patients were randomized to imetelstat (7.1 mg/kg by IV infusion) or placebo in 28-day treatment cycles until disease progression, unacceptable toxicity, or withdrawal from the study.1, 3 Baseline demographics were similar between the treatment groups, with the median age being 72 years, and the majority of patients classified as white (80%) and male (62%).1, 3 Patients in the imetelstat group were diagnosed a median of 3.5 years prior, and the majority had low-risk MDS (68%).1, 3 Similarly, patients in the placebo group were diagnosed a median of 2.8 years prior, and the majority had low-risk MDS (65%).1, 3 In both groups, the majority of patients had ring sideroblasts (62%).1 Transfusion burden was assessed at baseline; in both groups, approximately 54% of patients required ≥4 to ≤6 units over 8 weeks, while 46.5% of patients had a higher transfusion burden, requiring >6 units over 8 weeks.1, 3 The majority of patients (90%) were previously treated with an ESA.1, 3 Approximately 22% of imetelstat-treated patients and 37% of placebo-treated patients were ESA-ineligible.1, 3 A small proportion of patients (6.5%) were previously treated with luspatercept.1, 3
The primary end point was the proportion of patients who had RBC transfusion independence (RBC-TI) for ≥8 consecutive weeks.1, 3 A significantly greater proportion of imetelstat-treated patients (39.8%) achieved RBC-TI for ≥8 consecutive weeks compared to placebo-treated patients (15.0%).1, 3 The median duration of response was 51.6 weeks for patients in the imetelstat group who met the primary end point, but the median duration of response was only 5 weeks when all patients who received imetelstat were considered in the analysis.1, 9
Key secondary end points included the rate of 24-week RBC-TI, the duration of RBC-TI, and the rate of hematological response (i.e., hematological improvement-erythroid [HI-E] based on modified International Working Group [IWG] 2006 criteria and revised 2018 criteria).3 Of the imetelstat-treated patients, 28.0% achieved RBC-TI for ≥24 consecutive weeks compared to 3.3% of placebo-treated patients.1, 3 There was no evidence of a significant treatment effect on HI-E based on IWG 2006 criteria; however, imetelstat appeared favorable in an ad-hoc analysis of HI-E based on 2018 revised IWG criteria with 42.2% of imetelstat-treated patients demonstrating a response compared to 13.3% of placebo-treated patients.3, 9
Myelodysplastic syndromes are a group of myeloid diseases characterized by proliferation of myelodysplastic stem and progenitor cells, peripheral blood cytopenias, and risk of progression to acute myeloid leukemia.3 Disease is typically stratified into 5 risk groups (very low, low, intermediate, high, and very high) based on the IPSS.3, 4 The majority of patients with MDS also develop anemia, which eventually progresses to dependence on RBC transfusions, and thus decreased quality of life and increased mortality.3 There are limited treatment options for patients with MDS.9 The European Society of Medical Oncology (ESMO) states that RBC transfusions may be utilized as the sole treatment option for lower-risk MDS; however, repeated RBC transfusions are associated with chronic anemia and iron overload.4 Therefore, ESMO, the American Society of Hematology (ASH), and the American Society of Clinical Oncology (ASCO) recommend ESAs as first-line agents for patients with anemia in lower-risk MDS with serum erythropoietin levels ≤500 IU/L.4, 7 The ESMO guideline further suggests that ESA treatment is most effective in patients without del(5q) mutations and in those with little to no need for transfusions.4 Notably, treatment with ESAs does not impact disease progression, but has been demonstrated as an independent, favorable prognostic factor for survival.4 Second-line treatment options include antithymocyte globulin (as an off-label use), cyclophosphamide (as an off-label use), azacitidine, lenalidomide, and luspatercept.4 Imetelstat is not mentioned in these guidelines as the drug was approved after the guidelines were published.4, 7 Additional studies are needed to determine imetelstat's place of therapy in the treatment of MDS.1, 3, 4, 7
Administer imetelstat via IV infusion.1
Imetelstat is available as 47 mg and 188 mg single-dose vials of lyophilized powder.1 The sterile powder must be reconstituted and diluted prior to IV infusion.1
Store vials of imetelstat refrigerated at 2-8ºC in the original carton.1 Do not freeze.1
Remove the required number of vials from the refrigerator and allow them to sit at room temperature for 10-15 minutes (not to exceed 30 minutes) prior to reconstitution.1
Reconstitute 47 mg vials with 1.8 mL of 0.9% sodium chloride injection.1 Reconstitute 188 mg vials with 6.3 mL of 0.9% sodium chloride injection.1 The final concentration of each vial of reconstituted solution should be 31.4 mg/mL.1 Swirl each vial gently, avoiding foaming, until the powder is fully reconstituted (not to exceed 15 minutes); do not shake.1 The reconstituted solution should appear as a clear to slightly hazy solution.1 Visually inspect the solution for particulate matter and discoloration and do not use if present.1 Use the reconstituted solution immediately to prepare the diluted solution.1
Calculate the required volume of reconstituted imetelstat solution needed to obtain the appropriate dose according to the patient's body weight.1 Withdraw a volume equal to the required volume of reconstituted imetelstat solution from a 500 mL 0.9% sodium chloride infusion bag and discard it.1
Withdraw the required volume of reconstituted imetelstat solution from the vial(s) and add to the 0.9% sodium chloride infusion bag.1 The total final volume of the infusion bag should be 500 mL.1
Gently invert the infusion bag at least 5 times to ensure that the solution is well-mixed.1 Do not shake.1
Store prepared solution under refrigeration (2-8ºC) for 48 hours, including time from reconstitution to completion of IV infusion.1 Imetelstat may also be stored at room temperature (20-25ºC) for ≤18 hours, including time from reconstitution to completion of IV infusion.1
The prepared imetelstat solution is administered via IV infusion over 2 hours.1
Administration rate may be modified for infusion-related reactions, as described in Table 2.1
Dosage of imetelstat sodium is expressed in terms of imetelstat.1
For the treatment of MDS in adults with transfusion-dependent anemia requiring ≥4 red blood cell (RBC) units over 8 weeks who have not responded to, have lost response to, or are ineligible for erythropoiesis-stimulating agents (ESA), the recommended dosage of imetelstat is 7.1 mg/kg administered via IV infusion over 2 hours every 4 weeks.1
Discontinue imetelstat if patients do not experience a response (decrease in RBC transfusion burden) after 24 weeks of treatment or if unacceptable toxicity occurs.1
Dosage Modification for Hematologic Toxicity
Modify dosage for Grade 3-4 (as defined by National Cancer Institute Common Terminology for Adverse Events) hematologic adverse effects as described in Table 1.1, 5 When an initial dosage reduction is required, reduce the dose one level to 5.6 mg/kg.1 If a subsequent dosage level reduction is required, further reduce the dose to 4.4 mg/kg.1 Treatment should be permanently discontinued if the patient cannot tolerate the lowest dose level of 4.4 mg/kg.1
Adverse Reaction | Severity Grade | Imetelstat Dosage Modification |
|---|---|---|
Thrombocytopenia | Grade 3 (<50,000-25,000/mm3) | First occurrence: Delay imetelstat until recovery of platelets to 50,000/mm3; restart at same dose level. Second and third occurrence: Delay imetelstat until recovery of platelets to 50,000/mm3; restart at one dose level lower. Fourth occurrence: Discontinue imetelstat. |
Thrombocytopenia | Grade 4 (<25,000/mm3) | First and second occurrence: Delay imetelstat until recovery of platelets to 50,000/mm3; restart at one dose level lower. Third occurrence: Discontinue imetelstat. |
Neutropenia | Grade 3 (ANC <1000/mm3 with a single temperature of >38.3°C or or a sustained temperature of ≥38°C for >1 hour) | First occurrence: Delay imetelstat until recovery of ANC to 1000/mm3; restart at same dose level. Second and third occurrence: Delay imetelstat until recovery of ANC to 1000/mm3; restart at one dose level lower. Fourth occurrence: Discontinue imetelstat. |
Neutropenia | Grade 4 (Life-threatening consequences; urgent intervention indicated) | First and second occurrence: Delay imetelstat until recovery of platelets to 1000/mm3; restart at one dose level lower. Third occurrence: Discontinue imetelstat. |
Dosage Modification for Non-Hematologic Toxicity
Modify dosage for Grade 2-4 non-hematologic adverse effects as described in Table 2.1, 5 When an initial dosage reduction is required, reduce the dose one level to 5.6 mg/kg.1 If a subsequent dosage level reduction is required, further reduce the dose to 4.4 mg/kg.1 Treatment should be permanently discontinued if the patient cannot tolerate the lowest dose level of 4.4 mg/kg.1
Adverse Reaction | Severity Grade | Imetelstat Dosage Modification |
|---|---|---|
Infusion-Related Reactions | Grade 2 (Therapy or infusion interruption indicated but responds promptly to symptomatic treatment [e.g., antihistamines, NSAIDS, narcotics, IV fluids]; prophylactic medications indicated for ≤24 hrs) | First and second occurrence: Interrupt the imetelstat infusion until resolution of the adverse reaction or until the intensity of the reaction decreases to Grade 1; restart infusion at 50% of the infusion rate administered prior to the adverse reaction. Third occurrence: Stop infusion. May restart at next cycle. |
Infusion-Related Reactions | Grade 3 (Prolonged [e.g., not rapidly responsive to symptomatic medication and/or brief interruption of infusion]; recurrence of symptoms following initial improvement; hospitalization indicated for clinical sequelae) | First and second occurrence: Interrupt the imetelstat infusion until resolution of the adverse reaction or until the intensity of the reaction decreases to Grade 1; restart infusion at 50% of the infusion rate administered prior to the adverse reaction. Third occurrence: Permanently discontinue imetelstat. |
Infusion-Related Reactions | Grade 4 (Life-threatening consequences; urgent intervention indicated) | First occurrence: Stop infusion. Administer supportive care as appropriate and permanently discontinue imetelstat. |
Other adverse reactions, including elevated LFTs | Grade 3 or 4 | First and second occurrence: Delay imetelstat until recovery of adverse reactions to Grade 1 or baseline; restart at one dose level lower. Third occurrence: Permanently discontinue imetelstat. |
The manufacturer makes no specific dosage recommendations for patients with hepatic impairment.1
The manufacturer makes no specific dosage recommendations for patients with renal impairment.1
The manufacturer makes no specific dosage recommendations for geriatric patients.1
Imetelstat can cause thrombocytopenia.1 In the IMerge trial, thrombocytopenia was the most commonly reported treatment-emergent adverse event.3 In the imetelstat group, 75% of patients experienced thrombocytopenia (any grade), compared to 10% of patients in the placebo group.3 In imetelstat-treated patients, the majority of thrombocytopenia cases were Grade 3-4 (65%) and occurred during the first 3 treatment cycles.1, 3 The median duration of the thrombocytopenia event was 1.4 weeks, and the majority of cases (86%) resolved to Grade 2 or less within 4 weeks.3 Grade 3-4 bleeding events were similar in imetelstat- and placebo-treated patients.1, 3
Monitor complete blood counts prior to initiation of imetelstat, weekly for the first two cycles, prior to each cycle thereafter, and as clinically indicated.1
If thrombocytopenia occurs, monitor patient for bleeding, administer platelet transfusions as needed, and modify the dose or discontinue treatment as recommended in Table 1.1
Imetelstat can cause neutropenia.1 In the IMerge trial, neutropenia was the second most commonly reported treatment-emergent adverse event.3 In the imetelstat group, 74% of patients experienced neutropenia (any grade), compared to 7% of patients in the placebo group.3 In imetelstat-treated patients, the majority of neutropenia cases were Grade 3-4 (72%) and occurred during the first 3 treatment cycles, with a median time to onset of 4.6 weeks.1, 3 The median duration of the neutropenia event was 1.9 weeks, and the majority of cases (81%) resolved to grade 2 or less within 4 weeks.1, 3 Grade 3-4 infections and febrile neutropenia events were similar in imetelstat- and placebo-treated patients.1, 3
Monitor complete blood counts prior to initiation of imetelstat, weekly for the first two cycles, prior to each cycle thereafter, and as clinically indicated.1
If neutropenia occurs, monitor patient for infections, including sepsis, administer growth factors and anti-infective therapies as appropriate, and modify the dose or discontinue treatment as recommended in Table 1.1
Imetelstat can cause infusion-related reactions.1 In the IMerge trial, infusion-related reactions (of any severity) were reported in 8% of patients, and Grade 3-4 infusion-related reactions occurred in 1.7% of patients.1 The most commonly reported infusion-related reaction was headache (4.2%).1 Hypertensive crisis was also reported (0.8%).1
Premedicate patients at least 30 minutes prior to infusion with diphenhydramine and hydrocortisone as recommended and monitor patients for at least 1 hour following the infusion as recommended.1
If an infusion-related reaction occurs, manage symptoms with supportive care and infusion interruptions, decreased infusion rate, or permanent discontinuation, as described in Table 2.1
Fetal/Neonatal Morbidity and Mortality
Imetelstat can cause embryo-fetal harm when administered to a pregnant woman.1 In animal studies, imetelstat administration to pregnant mice during organogenesis resulted in embryo-fetal mortality at maternal exposures 2.5-times the human exposure at the recommended clinical dose.1
Advise pregnant women of the potential risk to a fetus.1
Advise females of reproductive potential to use effective contraception during treatment with imetelstat and for 1 week after the last dose.1
There are no available human data on imetelstat use in pregnant women.1 However, based on animal studies, imetelstat can cause embryo-fetal harm when administered to a pregnant woman.1 Imetelstat administration to pregnant mice during organogenesis resulted in embryo-fetal mortality at maternal exposures 2.5-times the human exposure at the recommended clinical dose.1
Advise pregnant women of the potential risk to a fetus.1
Advise females of reproductive potential to use effective contraception during treatment with imetelstat and for 1 week after the last dose.1
It is not known whether imetelstat is distributed into human milk.1 Effects of the drug on breastfed infants or milk production are also not known.1 However, because of the potential for adverse effects in breastfed children, advise women not to breastfeed during treatment with imetelstat and for 1 week after the last dose.1
Females and Males of Reproductive Potential
Based on animal studies, imetelstat can cause embryo-fetal harm when administered to a pregnant woman.1 Verify pregnancy status prior to initiating treatment with imetelstat.1
Advise females of reproductive potential to use effective contraception during treatment with imetelstat and for 1 week after the last dose.1
Based on animal studies, imetelstat may impair fertility in females of reproductive potential, though the effect is reversible.1
Safety and efficacy of imetelstat have not been established in pediatric patients <18 years of age.1
In the IMerge trial, the majority of patients (77.1%) were ≥65 years of age and 29.7% were ≥75 years of age.1 No differences in safety or efficacy were observed between older and younger patients.1
Mild (total bilirubin ≤ upper limit of normal [ULN] and AST >ULN, or total bilirubin >1- to 1.5-times ULN and any AST) and moderate hepatic impairment (total bilirubin >1.5- to 3-times ULN and any AST) do not appear to have a clinically important effect on the pharmacokinetics of imetelstat; however, the effects of severe hepatic impairment (total bilirubin >3x ULN and any AST) have not been established.1
Mild to moderate renal impairment (creatinine clearance 30 to <90 mL/minute) does not appear to have a clinically important effect on the pharmacokinetics of imetelstat; however, the effects of severe renal impairment (creatinine clearance 15 to <30 mL/minute) and end-stage renal disease have not been established.1
The most common adverse reactions (incidence ≥10% ), including laboratory abnormalities, reported with imetelstat in clinical studies were 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.1
Imetelstat is expected to be primarily metabolized by nucleases to nucleotides of various lengths.1
In vitro studies indicate that imetelstat does not inhibit or induce cytochrome P-450 (CYP) enzymes.1
In vitro studies indicate that imetelstat inhibits organic anion transporting polypeptide (OATP) 1B1 and OATP1B3.1
Imetelstat sodium is an oligonucleotide telomerase inhibitor.1, 3 Imetelstat exerts its effect by binding to the template region of the RNA component of human telomerase (hTR), inhibiting telomerase enzymatic activity, and preventing telomere binding.1, 3 In MDS, ineffective hematopoiesis is a result of dysfunctional malignant clone progenitor cells in the bone marrow.3 In typical myeloid progenitor cells, telomerase enables replication and prevents apoptosis.3 In malignant clone progenitor cells, high telomerase activity results in full clonal dominance in the bone marrow, leading to ineffective erythropoiesis.3 Imetelstat targets malignant progenitor cells with increased telomerase activity, and subsequently inhibits telomerase activity within the malignant cells, sparing the normal counterparts.3
Imetelstat does not accumulate between cycles.1 Imetelstat is >94% bound to plasma proteins.1 Imetelstat is expected to be primarily metabolized by nucleases to nucleotides of various lengths.1 The elimination half-life is approximately 4.9 hours.1
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
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.
Imetelstat is obtained through designated specialty pharmacies.6 Contact manufacturer or consult the imetelstat website ([Web]) for specific availability information.6
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | For injection, for IV use | 47 mg (of imetelstat) | Rytelo™ | Geron Corporation |
188 mg (of imetelstat) | Rytelo™ | Geron Corporation |
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions August 10, 2025. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
Only references cited for selected revisions after 1984 are available electronically.
1. Geron Corporation. RYTELO™ (imetelstat) injection prescribing information. Foster City, CA; 2024 June.
2. Food and Drug Administration. Search Orphan Drug Designations and Approvals. Silver Spring, MD. From FDA website. Accessed 2025 May 11.
3. Platzbecker U, Santini V, Fennaux, 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 Jan 20;403(10423):249-260.
4. Fenaux P, Haase D, Santini V, et al. Myelodysplastic syndromes: ESMO Clinical Practice Guidelines for diagnosis, treatment, and follow-up. Ann Oncol. 2021;32(2):142-156.
5. National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE). (Version 5). NCI. 2017.
6. How to Order Rytelo™. Accessed May 26, 2025. [Web]
7. Bohlius J, Bohlke K, Castelli R, et al. Management of cancer-associated anemia with erytropoiesis-stimulating agents: ASCO/ASH clinical practice guideline update. Blood Adv. 2019 Apr 23;3(8):1197-1210.
8. Celgene Corporation. REBLOZYL (luspatercept) injection prescribing information. Summit, NJ; 2023 Aug.
9. Food and Drug Administration. Center for Drug Evaluation and Research: Application number 217779Orig1s000: Multi-discipline review. From FDA website. [Web]