ENASIDENIB TAB
Clinical Criteria Summary
Exclusion Criteria
- Pregnancy (i.e., known pregnancy or positive pregnancy test) and/or actively breastfeeding
- Inability to swallow whole tablets
Inclusion Criteria
- Diagnosis of relapsed/refractory acute myeloid leukemia
- Defined as relapsed disease after 2 previous inductions OR
- Relapsed disease after 1 induction and not suitable for intensive chemotherapy
- Presence of an isocitrate dehydrogenase-2 (IDH2) mutation
- ECOG performance status 0-2
- For women of childbearing potential: Pregnancy must be excluded prior to receiving enasidenib; patient provided contraceptive counseling on potential risks vs. benefits if pregnancy occurs. Note may include men with female partners of childbearing potential if adequate contraception should be practiced.
Dosage and Administration
- Recommended starting dose: 100 mg taken orally once daily with or without food until disease progression or unacceptable toxicity
- Treat for a minimum of 6 months to allow time for clinical response (if no disease progression or unacceptable toxicity)
- Refer to Product Information for dosing modification based on adverse events
Monitoring
- Blood counts and blood chemistries for leukocytosis and tumor lysis syndrome prior to initiation; monitor at minimum every 2 weeks for at least the first 3 months during treatment
- Liver function tests including bilirubin level: evaluate at least monthly or when clinically indicated
- Pregnancy test (in women with childbearing potential) at baseline
- Monitor for signs and symptoms of differentiation syndrome (fever, cough, dyspnea, bone pain, rapid weight gain, edema, lymphadenopathy) and tumor lysis syndrome; differentiation syndrome noted as early as 10 days and up to 5 months after therapy initiation
Issues for Consideration
- FDA-approved indication: Treatment of adult patients with relapsed or refractory AML with an IDH2 mutation as detected by an FDA-approved test
- Off-label uses in other hematologic malignancies with IDH2-positive mutations require local adjudication processes
- Differentiation syndrome: Boxed warning highlights risk (reported in 14% of patients); if suspected, initiate oral or IV corticosteroids with hemodynamic monitoring until improvement
Renewal Criteria
- Documented benefit (defined as no disease progression or RBC and/or platelet transfusion independence)
- ECOG performance status has not declined to a level unacceptable to maintain quality of life