Active Ingredient: Imetelstat
Imetelstat 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).
For this indication, competent medicine agencies globally authorize below treatments:
For:
Intravenous, 7.1 milligrams imetelstat per kilogram of body weight, once every 4 weeks.
The recommended dosage of imetelstat is 7.1 mg/kg administered as an intravenous infusion over 2 hours every 4 weeks. Discontinue imetelstat 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.
Administer the following pre-treatment medications at least 30 minutes prior to dosing to prevent or reduce potential infusion-related reactions:
Monitor patients for adverse reactions for at least one hour after the infusion has been completed.
Recommended dose reductions for Grade 3 and Grade 4 adverse reactions are found in Table 1.
The management of Grade 3 and Grade 4 adverse reactions may require temporary dose delay, dose reduction, or treatment discontinuation and are presented in Table 2 and Table 3. Imetelstat treatment should be permanently discontinued if the patient cannot tolerate the lowest dose level of 4.4 mg/kg.
Table 1. Recommended Dose Reduction for Imetelstat for Grade 3 and Grade 4 Adverse Reactions:
| Dose Reduction | Dose Every 4 Weeks |
|---|---|
| First dose reduction | 5.6 mg/kg |
| Second dose reduction | 4.4 mg/kg |
Monitor complete blood cell counts prior to administration of imetelstat, weekly for the first two cycles, prior to each cycle thereafter, and as clinically indicated. Delay the next cycle if absolute neutrophil count is less than 1 × 109/L or platelets are less than 50 × 109/L. Modify dose as described in Table 2.
Table 2. Dosage Modifications for Patients with Hematologic Adverse Reactions (Grade 3 and Grade 4):
| Adverse Reaction | Severity Gradea | Occurrence | Treatment Modification |
|---|---|---|---|
| Thrombocytopenia | Grade 3 | First | Delay imetelstat until recovery of platelets to 50 × 109/L; restart at same dose level. |
| Second and Third | Delay imetelstat until recovery of platelets to 50 × 109/L; restart at one dose level lower. | ||
| Fourth | Discontinue imetelstat. | ||
| Grade 4 | First and Second | Delay imetelstat until recovery of platelets to 50 × 109/L; restart at one dose level lower. | |
| Third | Discontinue imetelstat. | ||
| Neutropenia | Grade 3 | First | Delay imetelstat until recovery of ANC to 1 × 109/L; restart at same dose level. |
| Second and Third | Delay imetelstat until recovery of ANC to 1 × 109/L; restart at one dose level lower. | ||
| Fourth | Discontinue imetelstat. | ||
| Grade 4 | First and Second | Delay imetelstat until recovery of ANC to 1 × 109/L; restart at one dose level lower. | |
| Third | Discontinue imetelstat. |
Abbreviation: ANC = absolute neutrophil count
a Severity based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03.
Dosage modifications for infusion-related reactions and other adverse drug reactions, including elevated liver function tests (LFTs), are described in Table 3. Monitor liver function tests prior to administration of imetelstat, weekly for the first cycle, prior to each cycle thereafter, and as clinically indicated.
Table 3. Dosage Modifications for Patients with Non-hematologic Adverse Reactions:
| Adverse Reaction | Severity Gradea | Occurrence | Treatment Modification |
|---|---|---|---|
| Infusion-Related Reactions | Grade 2 or 3 | First and Second | 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 | For Grade 2, stop infusion. May restart at next cycle. For Grade 3, permanently discontinue imetelstat. | ||
| Grade 4 | First | Stop infusion, administer supportive care as appropriate and permanently discontinue imetelstat. | |
| Other adverse reactions including elevated LFTs | Grade 3 or 4 | First and Second | Delay imetelstat until recovery of adverse reactions to Grade 1 or baseline; restart at one dose level lower. |
| Third | Permanently discontinue imetelstat. |
Abbreviation: LFT = liver function test
a Severity based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03.
Administer the imetelstat solution by intravenous infusion only over a period of 2 hours.
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