In an exciting development for patients and healthcare providers, the FDA has approved a new drug, RYTELO (Imetelstat), for the treatment of myelodysplastic syndromes (MDS).

This approval marks a significant advancement in the management of MDS, particularly for patients who have not responded to or are ineligible for other treatments.

Understanding Myelodysplastic Syndromes

Myelodysplastic syndromes (MDS) are a group of diverse bone marrow disorders in which the bone marrow does not produce enough healthy blood cells.

This can lead to symptoms such as fatigue, frequent infections, and bleeding complications. In some cases, MDS can progress to acute myeloid leukemia (AML), a more aggressive form of blood cancer. 

What is RYTELO (Imetelstat)?

RYTELO (imetelstat) is an oligonucleotide telomerase inhibitor. Telomerase is an enzyme that helps protect the ends of chromosomes during cell division, thus playing a role in cellular aging and cancer.

By inhibiting this enzyme, RYTELO aims to limit the uncontrolled proliferation of abnormal cells characteristic of MDS.

Indications for RYTELO (Imetelstat) Use:

RYTELO is specifically indicated for the treatment of adult patients with low- to intermediate-1 risk myelodysplastic syndromes who have transfusion-dependent anemia and require 4 or more red blood cell units over 8 weeks.

These patients typically have not responded to, or have lost response to, erythropoiesis-stimulating agents (ESA), making RYTELO a vital alternative treatment option.

RYTELO (Imetelstat) Dosage and Administration:

The recommended dosage of RYTELO is 7.1 mg/kg administered as an intravenous infusion over 2 hours every 4 weeks.

It is crucial to premedicate patients to prevent infusion-related reactions. This premedication typically includes diphenhydramine and hydrocortisone administered at least 30 minutes prior to the infusion.

Close monitoring is essential, with blood counts checked weekly for the first two cycles and before each subsequent cycle.

Potential Side Effects of RYTELO (Imetelstat):

As with any medication, RYTELO comes with potential side effects. Common adverse reactions (incidence ≥10%) include decreased platelets, decreased white blood cells, increased liver enzymes, fatigue, and headache.

Severe but less common side effects include thrombocytopenia and neutropenia, which necessitate close monitoring and possible dose adjustments.

Special Precautions When Prescribing RYTELO (Imetelstat):

• Thrombocytopenia:

Patients should be monitored for platelet counts, and treatment should be delayed or adjusted if severe thrombocytopenia occurs.

• Neutropenia:

Similar precautions should be taken for neutropenia, with regular blood counts to guide treatment modifications.

• Infusion-Related Reactions:

Premedication is recommended, and the infusion should be interrupted or slowed if reactions occur.

• Embryo-Fetal Toxicity:

RYTELO can cause harm to a fetus, so females of reproductive potential should use effective contraception during treatment.

Other Side Effects Reported by Patients in Clinical Trials:

• General:
  • Fatigue
• Musculoskeletal and connective tissue disorders:
  • Arthralgia/myalgia
• Infections and infestations:
  • COVID-19,
  • Urinary tract infection
• Nervous system disorders:
  • Headache,
  • Syncope
• Immune system disorders:
  • Infusion-related reactions
• Respiratory, thoracic, and mediastinal disorders:
  • Epistaxis
• Vascular disorders:
  • Hematoma
• Skin and subcutaneous tissue disorders:
  • Pruritus
• Cardiac disorders:
  • Atrial arrhythmia
• Injury, poisoning, and procedural complications:
  • Fractures

Mechanism of Action of Imetelstat:

Imetelstat is an oligonucleotide human telomerase inhibitor that binds to the template region of the RNA component of human telomerase (hTR).

It 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 that Imetelstat treatment reduced telomere length, malignant stem and progenitor cell proliferation, and the induction of apoptotic cell death.

Half-life Elimination:

• 4.9 hours

Metabolism:

It is metabolized by Nucleases to Nucleotides of various lengths.

Conclusion:

The approval of RYTELO represents a new hope for patients with MDS who have limited treatment options. Its ability to target telomerase activity offers a novel approach to managing this challenging condition.

Healthcare providers should carefully monitor patients for side effects and adjust dosages as necessary to ensure the best possible outcomes.

For more detailed information, including full prescribing guidelines, healthcare professionals can refer to the official prescribing information and consult with their peers to integrate RYTELO into their treatment protocols effectively.

Read: FDA Prescribing Information in Detail Here