INNV-51. Rapid response to encorafenib and binimetinib (Enc/Bini) in a patient with recurrent ganglioglioma with leptomeningeal spread

Abstract Our patient was a 20-year-old female when diagnosed with a left parietal WHO Grade III anaplastic ganglioglioma (AGG) with BRAFV600E mutation, APC rearrangement exon 16 and CDKN2A/B loss per next generation sequencing after presenting with decreased unilateral visual acuity. Initial treatment included surgical resection, followed by concurrent radiation and temozolomide (TMZ). She initiated anti-BRAFV600E therapy with dabrafenib and trametinib but was intolerant due to intractable flu-like symptoms including fever, rash and fatigue. She declined further therapy after three months. She then completed six months of adjuvant TMZ. Approximately four years after initial diagnosis, she was admitted for progressive symptoms including ocular seizures, cognitive decline, cranial nerve palsies, uncontrolled anxiety and pain. MRI imaging demonstrated a focus of parenchymal enhancement, and adjacent leptomeningeal and cranial nerve enhancement. Following subsequent clinical decline, lumbar puncture confirmed malignant cells and metronomic TMZ was started for two weeks. A supportive care-only approach was considered given her clinical deterioration, including progressive cognitive decline, deafness, and blindness. However, she and her family agreed to initiate treatment with Enc/Bini. Two weeks after starting the BRAF/MEK inhibitor combination, her clinical picture had significantly improved, and the regimen was tolerated with minimal nausea. Ocular and generalized seizures resolved with targeted treatment and transition to lacosamide. Follow up MRI, ten weeks after initiating treatment showed posterior hemisphere cortical and subcortical encephalomalacia, laminar necrosis, increased FLAIR signal, and improving enhancement along the cranial nerves consistent with inflammatory, treatment related changes considering her dramatic clinical improvement. Prior studies in patients with primary CNS tumors and brain metastases have demonstrated encouraging responses and overall tolerability with this regimen. To our knowledge, this represents the first documented case of a rapid and durable (four months to date) clinical and radiographic response to systemic BRAF-targeted therapy in a patient with recurrent-AGG and leptomeningeal spread.