Rezlidhia

Relapsed or refractory acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation, as detected by an FDA-approved test.

150 mg orally twice daily until disease progression or unacceptable toxicity
Swallow capsules whole; take with or without food
Minimum treatment duration to assess response: 6 months
Dose reduction: 150 mg once daily

Capsules: 150 mg

None listed.

• Differentiation Syndrome: Occurred in 19% (11% Grade 3+, including fatal cases). Median onset: 16 days (range 1-148). Symptoms include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural/pericardial effusion, edema, hypotension, rapid weight gain, and renal failure. Treat with dexamethasone 10 mg IV q12h and hydroxyurea if leukocytosis ≥25,000.
• QTc Prolongation: QTcF >500 ms in 5%. Monitor ECGs weekly × 3 weeks, then before each cycle. Correct electrolyte abnormalities before starting.
• GI Toxicity: Nausea, vomiting, diarrhea, mucositis common.
• Hepatotoxicity: Monitor LFTs.
• Embryo-Fetal Toxicity

Nausea (38%), fatigue (30%), arthralgia (25%), constipation (25%), mucositis (25%), leukocytosis (23%), dyspnea (22%), rash (22%), diarrhea (21%), transaminase increase (22%), febrile neutropenia (21%), differentiation syndrome (19%)

Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.

Consult the complete prescribing information for drug interactions, including effects on CYP enzymes, transporters, and concomitant medications that may require dose adjustments or monitoring.

Consult the full prescribing information for pregnancy-related considerations.

Refer to prescribing information for lactation guidance.

Pediatric safety and efficacy information is detailed in the full label.

Dose modifications for organ impairment are specified in the complete prescribing information.

Olutasidenib is a potent, selective, small-molecule inhibitor of mutant isocitrate dehydrogenase 1 (IDH1). Mutant IDH1 catalyzes reduction of α-ketoglutarate to the oncometabolite 2-hydroxyglutarate (2-HG), which inhibits α-KG-dependent enzymes involved in histone and DNA demethylation, resulting in epigenetic dysregulation and a block in myeloid differentiation. By inhibiting mutant IDH1, olutasidenib reduces 2-HG levels, restores normal cellular differentiation, and induces maturation of leukemic blasts.

Tmax: 2-4 hours. Half-life: approximately 55-65 hours. Protein binding: ~98%. Metabolized by CYP3A4 and esterases. Steady-state by ~2 weeks. Excreted in feces (~73%) and urine (~12%).

Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.

• Study 2102-02 — Olutasidenib in IDH1-mutated relapsed/refractory AML. Phase I/II, n=153.
  🔬 NCT02719574 ↗ 📄 Primary Publication ↗

Rezlidhia has FDA-approved indications across the following cancer types covered on PipelineEvidence: