Abstract Background MEK inhibitors are approved and widely used for the treatment of Neurofibromatosis type 1 (NF-1) associated plexiform neurofibromas (PN). We report an unanticipated decrease in cerebellar enhancement following a change in MEK inhibitors, resulting in deferral of planned surgical intervention in a young child with NF-1 and a presumed low-grade glioma. Case Report A7-year-old male with NF1, optic pathway glioma (OPG), and multiple PNs was treated with selumetinib for two enlarging PNs for 34 months. During therapy, one PN progressed on clinical examination and MRI, while surveillance imaging identified new patchy cerebellar enhancement concerning for a low-grade glioma. Treatment was switched from selumetinib to mirdametinib due to PN progression, and an elective surgical biopsy of the cerebellar lesion was planned. After two months of mirdametinib therapy, preoperative imaging demonstrated near-complete resolution of cerebellar enhancement, prompting the cancellation of the planned surgery. Conclusion This case demonstrates differential responses to two MEK inhibitors in an NF-1-associated cerebellar contrast-enhancing lesion suspected to be a low-grade glioma. Although both selumetinib and mirdametinib are approved for NF1-related PN, mirdametinib led to a marked reduction in enhancement and obviated planned surgical intervention. These findings suggest that a trial of different MEK inhibition may be considered prior to invasive procedures in select NF-1 patients, with continued long-term monitoring of radiographic response.
Pathare et al. (Tue,) studied this question.