Ivosidenib — Drug Monograph

Brand names: Tibsovo

Drug class: Other

Mechanism of Action

Targeted inhibitor of mutant IDH1 (isocitrate dehydrogenase 1). Mutant IDH1 aberrantly produces the oncometabolite 2-hydroxyglutarate (2-HG), which competitively inhibits alpha-ketoglutarate-dependent dioxygenases (including TET2, histone demethylases), causing epigenetic dysregulation and blocked cellular differentiation. Ivosidenib reduces 2-HG levels, restoring myeloid differentiation and inducing apoptosis of malignant clones.

FDA Indications

• Relapsed or refractory IDH1-mutated acute myeloid leukemia (AML) in adults (FDA approved July 2018; AG120-C-001: 30.8% CR+CRi rate)
• Newly diagnosed IDH1-mutated AML in adults ≥75 years or unfit for intensive induction (FDA approved May 2019)
• IDH1-mutated locally advanced or metastatic cholangiocarcinoma after prior therapy (FDA approved August 2021; ClarIDHy: improved PFS vs placebo)

Common Side Effects

• Nausea (30%)
• Diarrhea (24%)
• Fatigue (25%)
• QTc prolongation (14%)
• Edema (23%)
• Leukocytosis
• Arthralgia
• Increased bilirubin

Clinical Pearl

Ivosidenib uniquely treats both AML and cholangiocarcinoma via IDH1 mutation targeting, making it a paradigm for biomarker-driven therapy across histologies. Differentiation syndrome is the critical safety concern (black box warning), typically occurring 3–10 weeks after initiation and requiring prompt corticosteroid therapy. Do not delay steroid treatment while awaiting confirmatory imaging.

Related Therapies & Mechanisms

• Arsenic Trioxide (Trisenox) — Other · Leukemia
• Brexucabtagene autoleucel (Tecartus) — Other · Leukemia
• Enasidenib (Idhifa) — Other · Leukemia
• Glasdegib (Daurismo) — Other · Leukemia