P17.42.b Pemigatinib for Recurrent, Rapidly Progressive Dysembryoplastic Neuroepithelial Tumor: A Case Report

BACKGROUND Dysembryoplastic Neuroepithelial Tumor (DNT) was first described in the 1980s as novel glioneuronal tumors commonly presenting as a cause of drug-resistant epilepsy in early childhood. Most DNTs have singular, well-demarcated margins on imaging. Approximately 50% of DNTs show one or more small separate nodular subcortical lesions representing satellite lesions (SLs). Mutation or duplication of the tyrosine kinase domain of FGFR1 has been found in 60-80% of DNTs. Surgical resection is the standard of care for new diagnoses and recurrences. Alkylating chemotherapy has not shown any benefit. We report a 50-year-old male with a left occipitotemporal recurrent DNT, FGFR1-mutated, whom we treated with the FGFR protein kinase inhibitor, pemigatinib. CASE REPORT A 50-year-old man with a history of childhood epilepsy and occipital DNT resected in 2009 presented 15 years later with headache and gait instability. A head CT revealed acute hydrocephalus and a hemorrhagic lesion in the posterior left lateral ventricle. A brain MRI revealed a parenchymal enhancing lesion in the left occipital lobe and leptomeningeal disease. An initial CSF cytology after surgery was negative for neoplastic cells. The patient underwent repeat surgical resection and ventriculoperitoneal shunt placement. The tissue specimen showed an organizing hematoma with fragments of DNT. Next-generation sequencing was performed to test for rearrangements in 81 targeted genes including 104 known gene fusions and 29 abnormal gene transcript variants. FGFR 1 mutation was revealed, with an intact BRAF gene (Mayo Clinic Laboratories BRAFV). A repeat brain MRI showed a new enhancing lesion in the left anterior temporal lobe, with a bilateral subependymal spread in posterior and anterior horns. We recommended whole brain radiation therapy (WBRT). A brain MRI for radiation mapping after one month showed disease progression with a larger enhancing lesion in the left anterior temporal lobe and subependymal spread. Spine MRI and a second CSF cytology were negative. We proposed a change of strategy by deferring irradiation and instead targeting the FGFR mutation using pemigatinib. After a baseline ophthalmology evaluation, the patient took oral pemigatinib 13.5 mg in cycles, once daily for 14 consecutive days followed by 7 days off therapy. A brain MRI three and six months after the start of cycle one showed a complete response of the left anterior temporal lobe enhancing lesion and reduction of the subependymal enhancement (Fig 1D - F). He has tolerated pemigatinib after 9 cycles, with occasional grade 2 dizziness (NCTC v5) and serum phosphate within normal range. He has been seizure-free. CONCLUSION Although surgical resection remains the first-line treatment, FGFR inhibition using pemigatinib can serve as an alternate therapy for recurrent, refractory DNT.