Main Research Findings

Enasidenib is a newly approved drug for the treatment of acute myeloid leukemia (AML) patients with a mutation in the IDH2 gene. 4 , 7 . Enasidenib targets cells with mutant copies of isocitrate dehydrogenase-2 (IDH2) and inhibits the oncometabolite 2-hydroxyglutarte (2-HG) produced by the mutant IDH2. 7 . Clinical trials have shown that enasidenib is effective for patients with relapsed or refractory AML. 4 , 7 . Enasidenib is also effective for newly diagnosed AML patients who are not suitable for standard chemotherapy. 4 . Enasidenib has also been shown to be effective for children with D-2-hydroxyglutaric aciduria, a metabolic disorder caused by mutations in the IDH2 gene. 1 .

Reasons for side effects

Enasidenib specifically targets cells with mutations in the IDH2 gene. 7 . Therefore, it does not affect normal cells. 7 . However, enasidenib can cause side effects by affecting cells with mutations in the IDH2 gene. 7 .

Common side effects

Differentiation syndrome

The most common side effect of enasidenib is differentiation syndrome. 7 . Differentiation syndrome occurs when AML cells differentiate into normal cells. 7 . Differentiation syndrome may be accompanied by symptoms such as fever, rash, shortness of breath, muscle pain, joint pain, and gastrointestinal symptoms. 7 .

Hyperbilirubinemia

Enasidenib can cause hyperbilirubinemia. 1 . Hyperbilirubinemia is an increase in the bilirubin level in the blood. 1 . Bilirubin is a substance produced when red blood cells break down. 1 . Hyperbilirubinemia can cause jaundice, which is yellowing of the skin and whites of the eyes. 1 .

Other side effects

Enasidenib may cause side effects such as fatigue, nausea, vomiting, constipation, diarrhea, and loss of appetite. 4 , 7 . Enasidenib may also cause side effects such as increased liver enzyme levels and decreased blood lymphocyte counts. 4 , 7 .

Countermeasures for side effects

Differentiation syndrome

Differentiation syndrome can be treated by stopping enasidenib administration or administering drugs such as steroids. 7 .

Hyperbilirubinemia

Hyperbilirubinemia can be treated by reducing the dosage of enasidenib. 1 .

Other side effects

Other side effects can be treated by stopping enasidenib administration or by symptomatic treatment. 4 , 7 .

Comparison between studies

Commonalities in studies

All of these studies have shown that enasidenib is effective for AML patients with mutations in the IDH2 gene. 4 , 7 , 1 . All of these studies have also shown that enasidenib can cause side effects such as differentiation syndrome. 4 , 7 , 1 .

Differences in studies

These studies differ in the methods of administration and the subjects. 4 , 7 , 1 . For example, the study in 4 administered enasidenib to patients with relapsed or refractory AML, while the study in 1 administered enasidenib to children with D-2-hydroxyglutaric aciduria. 4 , 7 , 1 . In addition, 3 evaluated the combination therapy of enasidenib and azacitidine for patients with newly diagnosed IDH2 mutant-positive AML.

Precautions for real-world application

Enasidenib has been shown to be effective for AML patients with mutations in the IDH2 gene. 4 , 7 , 1 . However, enasidenib can cause side effects such as differentiation syndrome. 4 , 7 , 1 . Therefore, it is important to follow your doctor's instructions when taking enasidenib. 4 , 7 , 1 .

Limitations of current research

The long-term effects of enasidenib are still not fully understood. 4 , 7 , 1 . Further research is also needed on how effective enasidenib is in combination therapy with other AML drugs. 4 , 7 , 1 .

Future research directions

Further research is needed on the long-term effects and safety of enasidenib. 4 , 7 , 1 . Research is also needed on how effective enasidenib is in combination therapy with other AML drugs. 4 , 7 , 1 .

Conclusion

Enasidenib is a new treatment for AML patients with mutations in the IDH2 gene that has shown effectiveness. 4 , 7 , 1 . However, enasidenib can cause side effects such as differentiation syndrome. 4 , 7 , 1 . Therefore, it is important to follow your doctor's instructions when taking enasidenib. 4 , 7 , 1 .