Enasidenib is an isocitrate dehydrogenase-2 (IDH2) inhibitor indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) who harbor an IDH2 mutation. As a targeted therapeutic agent, enasidenib provides therapeutic benefits while also being associated with certain adverse reactions and medication-related 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 in severity.

Hematological abnormalities: Non-infectious leukocytosis (12%), which is linked to 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 disturbance (12%), which is usually not severe.

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

Serious Side Effects of Enasidenib Requiring Vigilance

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%), hepatic dysfunction, and multiple organ failure.

Embryofetal Toxicity

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

Pregnant women: Enasidenib is contraindicated in pregnant women, and pregnancy status must be confirmed before initiating treatment.

Contraception requirements: Women of childbearing potential 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 contraception during treatment and for 1 month after drug discontinuation.

Lactating women: Breastfeeding is prohibited during treatment and for 1 month after stopping enasidenib.

Tumor Lysis Syndrome

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

Before starting medication, evaluate blood cell counts and blood biochemical indicators (especially white blood cell count and uric acid level). After treatment initiation, monitor these indicators every 2 weeks for at least the first 3 months, and address abnormal findings promptly.

Other Serious 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: If bilirubin levels remain >3 times the upper limit of normal for ≥2 weeks without elevated transaminases, reduce the dose 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 Administration

Pre-Administration Evaluation

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

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

Pregnancy testing: All women of childbearing potential must undergo pregnancy testing before taking 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 every 2 weeks for at least 3 months.

Liver function: Focus on bilirubin levels.

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

Symptoms of differentiation syndrome: Particularly in the first few months of treatment.

Signs of tumor lysis syndrome: Such as hyperuricemia and electrolyte disturbances.