Imetelstat (Rytelo)

Number: 1063

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses imetelstat (Rytelo) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Note: Requires Precertification: 

Precertification of imetelstat (Rytelo) is required of all Aetna participating providers and members in applicable plan designs. For precertification of imetelstat (Rytelo), call (866) 752-7021 or fax (888) 267-3277. For Statement of Medical Necessity (SMN) precertification forms, see Specialty Pharmacy Precertification. 

1. Criteria for Initial Approval

   Myelodysplastic syndromes (MDS)

   Aetna considers imetelstat (Rytelo) medically necessary for treatment of lower risk (e.g., International Prognostic Scoring System-Revised [IPSS-R] very low, low, and intermediate risk) myelodysplastic syndromes (MDS) with transfusion-dependent anemia when both of the following criteria are met:

   1. Member meets one of the following:
      1. The member has not responded to, has lost response to, or is ineligible (e.g., serum erythropoietin (sEPO) greater than 500 mU/mL) for erythropoiesis-stimulating agents (ESAs); or
      2. The member has not responded to or has lost response to luspatercept-aamt (Reblozyl); and
   2. The member has been receiving regular red blood cell (RBC) transfusions as defined by greater than or equal to 4 units per 8 weeks.

   Aetna considers all other indications as experimental, investigational, or unproven.

2. Continuation of Therapy

   Aetna considers continuation of imetelstat (Rytelo) therapy medically necessary in members requesting authorization for an indication listed in the Criteria for Initial Approval section when both of the following criteria are met:

   1. The member has achieved or maintained a reduction in red blood cell transfusion burden; and
   2. The member has not experienced an unacceptable toxicity from Rytelo.

Dosage and Administration

Imetelstat is supplied as Rytelo 47 mg and 188 mg powder in a single-dose vial for reconstitution given by intravenous infusion.

Low- to Intermediate-1 Risk Myelodysplastic Syndromes (MDS)

• The recommended dosage of Rytelo is 7.1 mg/kg administered as an intravenous infusion over 2 hours every 4 weeks.
• Premedicate prior to dosing with Rytelo for potential infusion-related reactions.
• Refer to full prescribing information for Rytelo for preparation and administration instructions and for dosage modifications.

Source: Geron, 2024

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Code	Code Description

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Background

U.S. Food and Drug Administration (FDA)-Approved Indications 

• Rytelo is indicated for 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 (ESAs).

Compendial Uses

• Myelodysplastic syndromes (MDS)

Imetelstat is available as Rytelo (Geron Corporation), an oligonucleotide telomerase inhibitor for intravenous use. Rytelo binds to the template region of the RNA component of human telomerase (hTR), inhibits telomerase enzymatic activity and prevents telomere binding. There are reports of increased telomerase activity and human telomerase reverse transcriptase (hTERT) RNA expression in MDS and malignant stem and progenitor cells. In nonclinical studies, Rytelo treatment resulted in a a reduction of telomere length, reduction of malignant stem and progenitor cell proliferation, and induction of apoptic cell death (Geron, 2024).

According to the prescribing information, Rytelo carries the following warnings, precautions, and adverse reactions:

• Warnings and precautions:

  • Thrombocytopenia: Grade 3 and Grade 4 thrombocytopenia occurred; obtain complete blood cell counts prior to initiation of Rytelo, weekly for the first two cycles, and prior to each cycle thereafter to monitor. Delay or dose reduce as recommended.
  • Neutropenia: Grade 3 and Grade 4 neutropenia occurred; obtain complete blood cell counts prior to initiation of Rytelo, weekly for the first two cycles, and prior to each cycle thereafter to monitor. Delay or dose reduce as recommended.
  • Infusion-related reactions: Premedicate before infusion. Interrupt, decrease the rate of infusion, or permanently discontinue Rytelo based on severity.
  • Embryo-fetal toxicity: Can cause embryo-fetal harm. Advise females of reproductive potential of potential risk to a fetus and to use effective contraception.
    
    

• Adverse reactions: 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.

 On June 6, 2024, the U.S. Food and Drug Administration approved imetelstat (Rytelo) for the treatment of adults with low- to intermediate-1 risk myelodysplastic syndromes (MDS) with transfusion-dependent anemia requiring four 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 (ESAs). The FDA approval was based on supporting data from the IMerge study, a randomized, double-blind, placebo-controlled, multicenter, phase 3 trial (FDA, 2024).

In the IMerge study, Platzbecker and colleagues (2024) evaluated the efficacy of imetelstat (Rytelo) in 178 patients with International Prognostic Scoring System (IPSS) low- or intermediate-1 risk MDS who were transfusion-dependent (requiring ≥ 4 red blood cell (RBC) units over an 8-week period during the 16 weeks prior to randomization). Patients were eligible for this study if they had failed to respond or lost response or were ineligible for erythropoiesis-stimulating agents (ESAs); and had an absolute neutrophil count of 1.5 x 10⁹/L or greater and platelets 75 x 10⁹/L or greater. Patients were ineligible if they had del(5q) cytogenetic abnormality or had received prior treatment with lenalidomide or hypomethylating agents. Patient randomization was 2:1 to receive an intravenous infusion of Rytelo (n=118) 7.1 mg/kg over 2 hours or placebo (n=60) in 28-day treatment cycles until disease progression, unacceptable toxicity, or withdrawal from the study. The investigators stratified randomization by previous RBC transfusion burden and IPSS risk group. All patients received supportive care inclusive of RBC transfusions. Efficacy was established after a median follow up time of 19.5 months (range: 1.4 to 36.2) in the Rytelo group and 17.5 months (range: 0.7 to 34.3) in the placebo group based upon the proportion of patients who achieved ≥ 8-week and ≥ 24-week RBC transfusion independence (RBC-TI), defined as the absence of RBC transfusion(s) during any consecutive 8 week period, and during any consecutive 24 week period, respectively, from randomization until the start of subsequent anti-cancer therapy (if any). The rate of ≥ 8-week RBC-TI was 39.8% (95% Confidence Interval [CI]: 30.9,49.3) in the Rytelo group and 15% (95% CI: 7.1, 26.6) in the placebo group (p-value < 0.001).The rate of ≥ 24-week RBC-TI was 28% (95% CI: 20.1, 37) in the Rytelo group and 3.3% (95% CI: 0.4, 11.5) in the placebo group (p-value < 0.001) (FDA, 2024). Grade 3-4 treatment-emergent adverse events were noted in 91% (107/118) of patients receiving Rytelo and in 47% (28/59) of patients receiving placebo. The most common treatment-emergent grade 3-4 adverse events were neutropenia in the Rytelo group (80/118 [68%]) vs the placebo group (2/59 [3%]) and thrombocytopenia (73/118 [62%]) vs (5/59 [8%]), respectively. The investigators concluded that Rytelo treatment offers durable transfusion independence (approximately 1 year) and disease-modifying activity for heavily transfused patients with lower-risk MDS who are not responding to are ineligible for ESAs.

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References