10124-CS-11 Use of selumetinib in patients with neurofibromatosis type 1 and concomitant plexiform neurofibroma and low-grade glioma: a report of two cases

Abstract Neurofibromatosis type 1 (NF1) is a genetic disorder with diverse systemic manifestations. The MEK1/2 inhibitor selumetinib was approved in Japan in 2022 for symptomatic, inoperable plexiform neurofibromas (PNs). NF1 also predisposes individuals to pediatric low-grade gliomas (pLGGs). A Phase II trial has suggested selumetinib’s efficacy for recurrent/refractory pLGGs, and a Phase III trial for newly diagnosed cases is ongoing. We report on two NF1 patients with co-existing pLGG who received selumetinib primarily for symptomatic PNs. Case 1, an 11-year-old female, received selumetinib for severe PN-related pain. Her brain MRI showed a right optic pathway glioma (OPG) without visual impairment. The pain resolved by week 11, but an MRI at week 18 showed no significant change in OPG size. Case 2, a 14-year-old male with a history of a midbrain pilocytic astrocytoma (KIAA1549::BRAF fusion-positive), was started on selumetinib for pain from a newly diagnosed axillary PN. His pain improved by week 4; the glioma response is pending evaluation. In our cases, selumetinib showed a remarkable and early effect on PN-related pain, the primary therapeutic target. However, its short-term effect on co-existing pLGGs was either not significant or pending evaluation. As PNs and LGGs often coexist in NF1, a comprehensive assessment of all lesions is crucial during selumetinib treatment. This report highlights selumetinib’s potential as a systemic therapy for multiple NF1-related tumors, warranting further investigation.