Mirdametinib, an FDA-Approved MEK1/2 inhibitor for adult and pediatric NF1-associated plexiform neurofibromas.

Introduction: Neurofibromatosis type 1 (NF1) is an autosomal-dominant cancer predisposition syndrome that leads to the development of plexiform neurofibromas (PNs), which can cause significant morbidity and are at risk to transform into malignant peripheral nerve sheath tumors (MPNSTs). Targeted therapies such as mirdametinib, a selective oral MEK1/2 inhibitor, have offered new treatment options for patients with symptomatic, inoperable PNs.

Areas covered: This review summarizes the pathophysiology of NF1, the role of MEK inhibition, and the development of mirdametinib as a treatment for NF1-associated plexiform neurofibromas. Relevant literature was identified through PubMed searches using keywords related to NF1, plexiform neurofibromas, MEK inhibition, and mirdametinib. Key aspects discussed include mirdametinib's pharmacologic properties, clinical efficacy, safety profile, and comparison with other MEK inhibitors.

Expert opinion: Mirdametinib offers an effective, targeted, and orally available treatment for NF1-associated plexiform neurofibromas, with the added advantage of CNS penetration and durable clinical benefit. However, resistance and toxicity remain challenges, and future research should focus on optimizing patient selection and developing combination strategies to further expand its role in NF1-PN management.