Enasidenib is an oral medication used in oncology for certain blood cancers. It offers a targeted approach, focusing on specific cancer-driving mechanisms rather than broadly impacting cells throughout the body. Its development provides an additional option for patients.
Enasidenib: A Targeted Therapy
Enasidenib is a targeted therapy, designed to interfere with specific molecules involved in cancer cell growth, progression, and spread. Unlike traditional chemotherapy, which often affects both cancerous and healthy rapidly dividing cells, targeted therapies aim to be more precise, potentially leading to fewer side effects. Enasidenib specifically targets a genetic alteration known as the isocitrate dehydrogenase-2 (IDH2) mutation. This mutation is found in approximately 12-20% of adult patients with acute myeloid leukemia (AML) and leads to an abnormal protein that contributes to cancer development. Enasidenib works by inhibiting this mutant IDH2 enzyme. The medication received regulatory approval in the United States in August 2017.
How Enasidenib Works
The IDH2 enzyme plays a role in cellular metabolism. When the IDH2 gene is mutated, the enzyme gains an abnormal function, producing an oncometabolite called 2-hydroxyglutarate (2-HG) instead of its normal product. Elevated 2-HG levels disrupt normal cellular processes, particularly epigenetic regulation. This oncometabolite inhibits key enzymes responsible for removing chemical tags from DNA and histones, leading to hypermethylation. This hypermethylation prevents blood cells from maturing properly, causing immature, abnormal cells characteristic of leukemia to accumulate.
Enasidenib acts as a selective inhibitor of the mutant IDH2 enzyme. By binding to the mutant enzyme, it reduces the production of 2-HG. This reduction helps to restore normal epigenetic regulation. As a result, blocked differentiation pathways are reactivated, allowing immature cancer cells to mature into healthy, functional blood cells. This mechanism means enasidenib primarily functions as a differentiation agent rather than a cytotoxic drug that directly kills cancer cells.
Conditions and Patient Eligibility
Enasidenib is specifically indicated for the treatment of acute myeloid leukemia (AML) in adult patients. Its use is restricted to those whose AML carries the isocitrate dehydrogenase-2 (IDH2) mutation, present in 12% to 20% of AML cases. Before treatment, genetic testing is required. An FDA-approved molecular diagnostic test detects the IDH2 mutation in a patient’s blood or bone marrow. Enasidenib is approved for patients with relapsed or refractory AML, meaning the cancer has returned or has not responded to previous therapies.
Managing Treatment
Enasidenib is administered orally as a tablet, typically once daily. The recommended dose is 100 milligrams, taken until disease progression or unacceptable side effects occur. For patients without progression or intolerable side effects, treatment should continue for at least six months for a potential clinical response. Regular monitoring by healthcare professionals is important, including frequent blood tests every two weeks for the first three months, to track blood counts and monitor for side effects.
Differentiation syndrome is a notable side effect, which can occur from 10 days to five months after starting treatment. Symptoms include fever, cough, trouble breathing, bone pain, rapid weight gain, or swelling in the arms, legs, or around the neck, groin, or underarms. Other common side effects include nausea, vomiting, diarrhea, and elevated bilirubin levels, which can cause yellowing of the skin or eyes (jaundice). Fatigue and decreased appetite are also frequently reported. Management of side effects, particularly differentiation syndrome, often involves systemic corticosteroids and close monitoring.