Enasidenib Dose Adjustments
1. Hepatotoxicity Management
Bilirubin elevation (more than 3 times the upper limit of normal lasting for 2 weeks or longer, without concomitant transaminase elevation or other hepatic disease):
(1) Reduce the dose to 50 mg daily.
(2) When the bilirubin elevation decreases to below 2 times the upper limit of normal, resume the 100 mg daily dose.
2. Differentiation Syndrome
(1) If differentiation syndrome is suspected, immediately administer systemic corticosteroids and perform hemodynamic monitoring.
(2) If severe pulmonary symptoms requiring intubation or ventilator support and/or renal dysfunction persist after 48 hours of corticosteroid initiation, interrupt enasidenib treatment.
(3) When symptoms and signs improve to Grade 2 or lower, treatment may be resumed.
3. Non-Infectious Leukocytosis [White Blood Cell (WBC) Count Greater Than 30x10⁹/L]
(1) Initiate hydroxyurea therapy per institutional standard operating procedures.
(2) If leukocytosis does not improve with hydroxyurea, interrupt enasidenib treatment. When the WBC count decreases to below 30x10⁹/L, resume enasidenib at the 100 mg daily dose.
4. Other Treatment-Related Grade 3 or Higher Toxicities (e.g., Tumor Lysis Syndrome)
(1) Interrupt treatment until the toxicity resolves to Grade 2 or lower.
(2) Upon resuming treatment, adjust the dose to 50 mg daily; if the toxicity resolves to Grade 1 or lower, the dose may be increased to 100 mg daily.
(3) If Grade 3 or higher toxicity recurs, permanently discontinue enasidenib.
Enasidenib Precautions
U.S. Boxed Warning: Patients receiving enasidenib may experience symptoms of differentiation syndrome, which can be fatal if not treated promptly. Symptoms may include fever, dyspnea, acute respiratory distress, pulmonary infiltrates, pleural or pericardial effusion, rapid weight gain or peripheral edema, lymphadenopathy, bone pain, and hepatic, renal, or multiorgan dysfunction. If differentiation syndrome is suspected, immediately initiate corticosteroid therapy and hemodynamic monitoring until symptoms resolve.
