OLUTASIDENIB CAP,ORAL
Clinical Criteria Summary
Document 485
Exclusion Criteria
- Severe renal impairment (defined as CrCl < 30 ml/min)
- Severe hepatic impairment (defined as total bilirubin > 3x Upper limit of normal and any AST)
- Chronic or unresolved infection
- Unmanageable drug interaction
- Pregnancy
- Breastfeeding
Inclusion Criteria
- Care provided by a VA/VA Community Care hematology/oncology provider
- Goals of care and role of Palliative Care consult have been discussed and documented
- ECOG performance status 0-2
- Presence of an isocitrate dehydrogenase-1 (IDH-1) mutation
- Diagnosis of relapsed or refractory acute myeloid leukemia
Reproductive Health & Counseling Requirements
- Pregnancy must be excluded prior to receiving olutasidenib
- Patient must receive contraceptive counseling on potential risks vs. benefits of taking olutasidenib if pregnancy occurs during treatment
- Breastfeeding is contraindicated during treatment and for at least 2 weeks after the last dose
Document 486
Indication & Patient Selection
- Treatment of relapsed or refractory AML with susceptible IDH1 mutation
- Adults aged > 18 years
- ECOG PS 0-2
- QT-interval < 450 ms
- Presence of the IDH1 mutation from blood or marrow sample must be confirmed prior to therapy
- Excluded: patients with symptomatic CNS leukemia, uncontrolled infection or metabolic disorders, prior IDH inhibitor therapy
Dosing & Administration
- 150 mg orally twice daily until disease progression, toxicity or HSCT
- Cycle = 28-days
Monitoring & Safety Requirements
- Differentiation syndrome: If suspected, hold olutasidenib, initiate corticosteroids and hemodynamic monitoring until symptom resolution
- Hepatotoxicity: Monitor LFTs at baseline, at least once weekly x 2 months; every other week for 3rd month; once in 4th month, and every other month for remainder of therapy. May need to interrupt, hold or discontinue therapy.
- Adverse reactions > 20% include: ↑AST, ↑ALT, ↓potassium, ↓sodium, ↑alk phos, nausea, ↑SCr, fatigue, arthralgia, constipation, ↑lymphocytes, ↑T bili, leukocytosis, ↑uric acid, dyspnea, pyrexia, rash, ↑lipase, mucositis, diarrhea, transaminitis
Contraindications & Precautions
- Contraindications: None
- Boxed warning: Differentiation syndrome (Noted in 16%, gr 3-4 in 8%)
- Warnings/Precautions: Hepatotoxicity (Noted in 23%, gr 3-4 in 13%)
Pregnancy & Lactation
- Avoid in pregnancy; may cause fetal harm
- Avoid breastfeeding during therapy and for 2 weeks after last dose
Drug Interactions
- Avoid strong or moderate CYP3A4 inducers
- Avoid sensitive CYP3A substrates; if unavoidable, monitor for loss of substrate effect
Place in Therapy/Additional Notes
- Second FDA-approved IDH1 inhibitor for treatment of IDH1-mutated relapsed/refractory AML
- Not FDA-approved in combination with a hypomethylating agent (i.e., azacitidine, decitabine)