Enasidenib is an isocitrate dehydrogenase-2 (IDH2) inhibitor used to treat adult patients with relapsed or refractory acute myeloid leukemia (AML) who have an IDH2 mutation. As a targeted therapy, enasidenib provides therapeutic effects while also carrying certain adverse reactions and medication risks.

What Are the Side Effects of Enasidenib?

Common Side Effects

Gastrointestinal Reactions: Gastrointestinal symptoms such as nausea (50%), vomiting (34%), diarrhea (43%), and decreased appetite (34%) are relatively common, and most are mild to moderate.

Hematological Abnormalities: Non-infectious leukocytosis (12%), which is associated with drug-induced bone marrow proliferation.

Metabolic Abnormalities: Electrolyte disturbances including elevated blood bilirubin (81%), decreased blood calcium (74%), and decreased blood potassium (41%).

Neurological Symptoms: Taste disorders (12%), which are usually not severe.

Other Reactions: Systemic symptoms such as fatigue, fever, and weight loss.

Severe Side Effects of Enasidenib to Watch For

Differentiation Syndrome

Differentiation syndrome is the most serious complication during enasidenib treatment, with an incidence of approximately 14% and potential life-threatening risks.

Characteristic Manifestations Include:

Respiratory Symptoms: Dyspnea (68%), hypoxemia (76%), acute respiratory distress, pulmonary infiltrates (73%), and pleural effusion (45%).

Systemic Symptoms: Fever (36%), peripheral edema with rapid weight gain (21%), and lymphadenopathy (33%).

Organ Dysfunction: Renal impairment (70%), liver dysfunction, and multiple organ failure.

Embryo-Fetal Toxicity

Animal studies have shown that enasidenib can cause embryo-fetal death and growth abnormalities at doses equivalent to 0.1 times the human steady-state exposure.

Pregnant Women: Enasidenib is contraindicated; pregnancy status must be confirmed before medication use.

Contraception Requirements: Women of childbearing age should use effective contraceptive measures during treatment and for at least 1 month after discontinuing the drug. Male patients with reproductive partners should also use contraceptive measures during treatment and for 1 month after discontinuation.

Lactating Women: Breastfeeding is prohibited during treatment and for 1 month after discontinuing the drug.

Tumor Lysis Syndrome

Enasidenib may induce rapid reduction of tumor cells through promoting bone marrow proliferation, thereby triggering tumor lysis syndrome.

Before medication use, it is necessary to evaluate blood cell counts and blood biochemical indicators (especially white blood cell count and uric acid level). After starting treatment, monitoring should be conducted every 2 weeks for at least the first 3 months, and abnormal conditions should be addressed promptly.

Other Severe Reactions

Non-infectious Leukocytosis: Intervention is required when the white blood cell count exceeds 30×10⁹/L; treatment with hydroxyurea may be considered.

Elevated Bilirubin: When bilirubin remains ≥3 times the upper limit of normal for 2 weeks or more without elevated transaminases, the dose should be reduced to 50mg per day.

QT Interval Prolongation: Although no significant QT interval prolongation caused by enasidenib was observed in clinical trials, monitoring is still necessary.

Precautions for Enasidenib Use

Pre-Medication Assessment

Genetic Testing: IDH2 mutation must be confirmed using an FDA-approved testing method.

Baseline Examinations: Include complete blood count, blood biochemistry (with focus on white blood cell count, bilirubin, electrolytes, etc.), and electrocardiogram.

Pregnancy Testing: All women of childbearing age must undergo pregnancy testing before using the drug.

Drug Interactions

Hormonal Contraceptives: Enasidenib may alter their concentrations; additional or alternative contraceptive methods are recommended.

CYP3A4 Substrate Drugs: Their concentrations may be affected, requiring close monitoring.

UGT1A1 Substrate Drugs: Such as irinotecan, which may increase the risk of toxicity.

Patient Monitoring and Follow-Up

Hematological Indicators: Monitor at least every 2 weeks for a minimum of 3 months.

Liver Function: Focus on bilirubin levels.

Electrolytes: Especially ions such as calcium, phosphorus, and potassium.

Symptoms of Differentiation Syndrome: Particularly within the first few months of treatment.

Signs of Tumor Lysis Syndrome: Such as hyperuricemia and electrolyte disturbances.