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Differentiation Syndrome in a Patient With NSCLC Harboring IDH2 Mutation Treated With Enasidenib: Case Report
Bhoomika Sukhadia1,2, Dean Tan1, Youjin Oh1
1Division of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Abstract:
IDH2 gain-of-function mutations cause DNA hypermethylation interfering with cellular differentiation and are linked to poor disease outcomes in NSCLC. IDH2-inhibitor enasidenib is approved for refractory acute myeloid leukemia but has been associated with delayed onset of differentiation syndrome-a potentially fatal inflammatory reaction caused by differentiating agents, namely all-trans retinoic acid and arsenic trioxide. We report the first case of differentiation syndrome in a patient with NSCLC treated with enasidenib, who after 7 weeks experienced bilateral peripheral edema and shortness of breath, with scans exhibiting pericardial effusion and ground-glass opacities suggestive of pneumonitis. Differentiation syndrome should be considered as a differential diagnosis in patients with solid tumors undergoing IDH2-inhibitor targeted therapy.
Insights
Isocitrate dehydrogenase 2 (IDH2) inhibitors like enasidenib can cause differentiation syndrome in non-small cell lung cancer (NSCLC) patients. This potentially fatal inflammatory reaction requires careful monitoring during IDH2-targeted therapy.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Isocitrate dehydrogenase 2 (IDH2) gain-of-function mutations are implicated in non-small cell lung cancer (NSCLC) pathogenesis, leading to DNA hypermethylation and poor prognosis.
- Enasidenib, an IDH2 inhibitor, is approved for acute myeloid leukemia and is known to cause differentiation syndrome, a severe inflammatory response.
Observation:
- This report details the first documented case of differentiation syndrome in an NSCLC patient treated with enasidenib.
- The patient developed symptoms including bilateral peripheral edema, shortness of breath, pericardial effusion, and pneumonitis after seven weeks of treatment.
Findings:
- The observed symptoms in the NSCLC patient are consistent with differentiation syndrome, a known but rare side effect of IDH2 inhibitors.
- This case highlights that differentiation syndrome can occur in solid tumors, not just hematological malignancies.
Implications:
- Differentiation syndrome should be considered in the differential diagnosis for NSCLC patients receiving IDH2-inhibitor therapy.
- This finding underscores the need for vigilant monitoring and prompt management of potential inflammatory reactions in patients undergoing targeted IDH2 inhibition for solid tumors.
