ID #368 Successful Addition of Trametinib to Vinblastine Therapy for Three Patients with Low-Grade Glioma

Abstract Background Pediatric low-grade glioma is one of the most common pediatric tumors and has an excellent survival rate. The current standard of care is weekly vinblastine therapy. We present three patients with low-grade glioma who responded to vinblastine with trametinib therapy. Methods Retrospective chart review of three cases of low-grade glioma treated with vinblastine and trametinib. Results Patient 1 presented at age 4 with exotropia and low vision and had a large suprasellar mass compressing the right optic nerve. Biopsy showed pilocytic astrocytoma that was BRAF-V600E negative and FGFR positive. After two months of vinblastine, tumor was 41% larger. Trametinib was added to the vinblastine and 3 months following there was a 42% decrease in size, and it remains stable 2 years since diagnosis. Patient 2 (history of NF1) presented at age 2 with rapid onset proptosis. Imaging showed a fusiform lesion of the left optic nerve. She began vinblastine and 2 months later had a 40% increase in lesion size. Trametinib was added and follow up imaging showed a 50% decrease in the size of the lesion, and the proptosis improved. The lesion remains stable 20 months since diagnosis. Patient 3 presented at the age of 17 with headaches and papilledema and was found to have ventricular dilatation as well as abnormal leptomeningeal enhancement in the brain and spinal canal, with multiple enhancing nodules. Biopsy revealed disseminated low-grade glioma/pilocytic astrocytoma with FGFR, NF1pS1355 and PTPN mutations. He was and started on vinblastine and trametinib was added 3 months later. The lesions remain stable on imaging 9 months since diagnosis. Conclusions The addition of trametinib to vinblastine for low-grade glioma resulted in a decrease in tumor in two patients and stabilization in one. This combination of therapy should be further studied in a larger study.