IMETELSTAT INJ,LYPHL
Clinical Criteria Summary
Document 766
Exclusion Criteria
- Concurrent use of erythropoiesis stimulating agents (ESAs)
- Platelet count less than 75 x 109/L
- Absolute neutrophil count less than 1.5 x 109/L unless with Duffy Null phenotype
- Severe hepatic impairment defined as total bilirubin > 3x upper limit of normal (ULN) unless with Gilbert syndrome
- Severe renal impairment defined as serum creatinine < 30 ml/min
- Deletion 5q (del[5q]) karyotype
- Myelodysplastic syndromes / myeloproliferative neoplasm overlap syndrome
- Known pregnancy
- Lactation
Inclusion Criteria
- Confirmed diagnosis of low- to intermediate-1 risk myelodysplastic syndrome (MDS)
- Transfusion-dependent, requiring regular red blood cell (RBC) transfusions of ≥4 RBC units over 8 weeks
- Documentation of inadequate response, loss of response, intolerance or contraindication to an 8-week course of an erythropoiesis stimulating agent (ESA)
- Documentation of inadequate response, loss of response, intolerance or contraindication to a 9-week course of luspatercept-aamt at maximal tolerated doses (i.e. 1.75 mg/kg subcutaneously every 3 weeks)
Additional Inclusion Criteria
- For females who can become pregnant: Pregnancy should be excluded prior to receiving imetelstat
- For females who can become pregnant: Counseling provided on potential risks vs. benefits of treatment and the use of effective contraception during therapy and for 1 week after stopping treatment
- For lactating females: Advise against breastfeeding during treatment and for 1 week after the last dose
Document 767
Indication & Patient Population
- Adults with low- to intermediate-1 risk myelodysplastic syndromes (MDS)
- Transfusion-dependent anemia requiring four or more red blood cell units over 8 weeks
- Patients who have not responded to, lost response to, or are ineligible for erythropoiesis-stimulating agents (ESAs)
Dosing & Administration
- 7.1 mg/kg IV over 2 hours every 4 weeks
- Continue until progressive disease or unacceptable toxicity
Line of Therapy & Treatment Sequence
- Not a first-line (1L) treatment
- May serve as second-line (2L) or third-line (3L) therapy
- Recommended for patients who have not previously used imetelstat
Clinical Subgroups & Biomarkers
- Low or intermediate-1 risk disease per International Prognostic Scoring System (IPSS)
- Endogenous erythropoietin concentration >500 mU/mL
- Non-del(5q) MDS
- Applicable regardless of ring sideroblasts (RS) status or high transfusion burden
Safety & Clinical Considerations
- High rates of grade 3–4 neutropenia and thrombocytopenia observed; associated with higher need for cytopenia treatments and higher rates of infections and hemorrhagic events
- Embryofetal toxicity warning present
- Not recommended for myelofibrosis (current use is off-label; awaiting phase III trial results)