Dosage and Administration Guidelines for Asciminib

The recommended dosage of asciminib should be determined through comprehensive evaluation based on factors including the patient's disease phase (e.g., chronic phase or accelerated phase), response to prior therapy, presence of specific gene mutations (e.g., T315I mutation), and tolerability.

Philadelphia Chromosome-Positive Chronic Myeloid Leukemia in Chronic Phase (Ph+CML-CP)

Ph+CML-CP in Patients Previously Treated with Two or More Tyrosine Kinase Inhibitors (TKIs)

Recommended dosage: 80 mg orally once daily, or 40 mg orally every 12 hours.

Duration of treatment: Continue therapy as long as clinical benefit is observed until unacceptable toxicity occurs.

Ph+CML-CP with T315I Mutation

Recommended dosage: 200 mg orally every 12 hours.

Renal Dosage Adjustment

Mild to severe renal impairment (eGFR 15–89 mL/min/1.73 m²): No dosage adjustment required.

End-stage renal disease (eGFR <15 mL/min/1.73 m²): No relevant data available.

Hepatic Dosage Adjustment

Mild to severe hepatic impairment: No dosage adjustment required.

Dosage Modifications

Dose Reduction for Adverse Reactions

Ph+CML-CP Previously Treated with Two or More TKIs

First dose reduction: 40 mg orally once daily, or 20 mg orally twice daily.

Subsequent dose reduction: Permanently discontinue treatment in patients unable to tolerate the reduced dosage.

Ph+CML-CP with T315I Mutation

First dose reduction: 160 mg orally twice daily.

Subsequent dose reduction: Permanently discontinue treatment in patients unable to tolerate the reduced dosage.

Thrombocytopenia and/or Neutropenia

When absolute neutrophil count (ANC) <1 × 10⁹/L and/or platelet count (PLT) <50 × 10⁹/L:

Interrupt treatment until ANC recovers to ≥1 × 10⁹/L and/or PLT recovers to ≥50 × 10⁹/L.

If recovery occurs within 2 weeks: Resume treatment at the starting dosage.

If recovery takes longer than 2 weeks: Resume treatment at the reduced dosage.

For recurrent severe thrombocytopenia and/or neutropenia, interrupt treatment until ANC ≥1 × 10⁹/L and PLT ≥50 × 10⁹/L, then resume treatment at the reduced dosage.

Asymptomatic Elevations in Amylase and/or Lipase

When elevation >2 × upper limit of normal (ULN):

Interrupt treatment until levels recover to <1.5 × ULN.

If recovery occurs: Resume treatment at the reduced dosage; if the event recurs after dose reduction, permanently discontinue treatment.

If no recovery: Permanently discontinue treatment and perform diagnostic testing to rule out pancreatitis.

Non-Hematologic Adverse Reactions

For adverse reactions of Grade 3 or higher:

Interrupt treatment until recovery to Grade 1 or lower.

If recovery occurs: Resume treatment at the reduced dosage.

If no recovery: Permanently discontinue treatment.