Differentiation Syndrome in a Patient With NSCLC Harboring IDH2 Mutation Treated With Enasidenib: Case Report

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.