Revuforj (revumenib) is a novel menin inhibitor that was approved in the United States in 2024 for the treatment of relapsed or refractory acute leukemia harboring KMT2A gene translocation (in adults and children aged 1 year and older). As a targeted therapeutic agent, its efficacy and safety are highly dependent on standardized medication management and monitoring.
Precautions for Revuforj (Revumenib) Administration
Contraindicated Populations and Special Warnings
Risk of Differentiation Syndrome (DS): Approximately 29% of patients may experience DS symptoms such as fever, dyspnea, and hypotension; severe cases can be life-threatening. Before treatment, the white blood cell (WBC) count must be reduced to <25 Gi/L. Upon the onset of symptoms, glucocorticoids should be administered immediately and medication should be suspended.
QT Interval Prolongation: QT prolongation occurs in 29% of patients, with 12% experiencing grade 3 prolongation. Concomitant use of other QT-prolonging drugs should be avoided. Regular monitoring of electrocardiograms (ECG) and electrolytes is required during treatment.
Embryotoxicity: Animal studies have shown teratogenicity. Patients of childbearing potential must use effective contraceptive measures during treatment and for 4 months after the last dose. Revuforj is contraindicated during lactation.
Optimization of Dosing Regimen
Body Weight ≥ 40 kg: The baseline dose is 270 mg twice daily (when not used with strong CYP3A4 inhibitors) or 160 mg twice daily (when used concomitantly with strong CYP3A4 inhibitors).
Body Weight < 40 kg: The dose is adjusted based on body surface area (BSA). Tablets of different strengths (25 mg/110 mg/160 mg) must be combined to achieve precise dosing.
Dosing Timing: Administer orally at fixed times daily, either on an empty stomach or with a low-fat meal (≤25% fat content). If a dose is missed, it should be supplemented within 12 hours; double dosing is strictly avoided.
Management of Drug Interactions
Strong CYP3A4 Inhibitors (e.g., posaconazole): The dose needs to be reduced to 160 mg twice daily (for adults), as these inhibitors can double the plasma concentration of revumenib.
Strong/Moderate CYP3A4 Inducers (e.g., rifampicin): Concomitant use is contraindicated, as this may lead to reduced efficacy of revumenib.
QT-Prolonging Drugs (e.g., fluoroquinolones): If concomitant use is necessary, enhanced ECG monitoring is required.
Monitoring for Revuforj (Revumenib) Administration
Baseline Assessment
Genetic Testing: Confirm the presence of KMT2A translocation (no companion diagnostic reagent is available currently).
Laboratory Tests: Complete blood count, electrolytes (potassium/magnesium), liver function tests, ECG (QTc must be <450 ms), and bone marrow aspiration.
Intreatment Monitoring
Differentiation Syndrome (DS): Focused monitoring is required during the early treatment phase (Days 3–41). Upon symptom onset, the patient must be hospitalized immediately and receive intravenous dexamethasone.
Cardiotoxicity: ECG monitoring should be performed once weekly for the first month, then once monthly thereafter.
QTc Prolongation: Suspend medication if QTc > 480 ms; permanent discontinuation is required if QTc > 500 ms.
Metabolic Abnormalities: Monitor serum phosphorus, parathyroid hormone (elevated in 30% of patients), and blood lipids monthly.
Infection and Bleeding: Infection occurs in 41% of patients (20% are bacterial infections), and bleeding occurs in 53% of patients (9% are grade 3 or higher). Regular assessment is necessary.
