To report novel therapy with selumetinib in a patient with Neurofibomatosis type 2 (NF2) and associated tumors with partial response.

NF2 is diagnosed clinically or genetically by mutation in the NF2 tumor suppressor gene. Defective Merlin protein leads to overactivation of the Mitogen-activated protein kinase (MEK) pathway and parallel mammalian target of rapamycin (mTOR) pathway.

Limited targeted therapy exists for NF2 associated tumors but includes everolimus (mTOR inhibitor). Selumetinib is a MEK inhibitor with limited central nervous system (CNS) penetration. We present a case of medical therapy for NF2-associated tumors with everolimus and selumetinib. 

Case Report

A 25-year-old male with a clinical diagnosis of NF2 presented with multiple tumors including bilateral vestibular schwannomas, spinal cord intramedullary ependymomas, cranial and spinal meningiomas, spinal nerve root mixed schwannoma-neurofibromas, and spinal peripheral nerve sheath tumors. He tested negative for germline NF2, SMARCB1, and LZTR1 mutations. Molecular analysis of the resected cervical spinal compressive schwannoma-neurofibroma demonstrated an isolated somatic SMARCB1 mutation. Due to progression of all nervous system tumors, he was treated medically with both everolimus (10 mg/day) and selumetinib (25 mg/kg BID), but rapidly transitioned to selumetinib monotherapy due to drug toxicities. Treatment resulted in a partial response in one spinal ependymoma and stable disease in other tumors at 3 months.

Although the tumor lacked somatic NF2 mutation, SMARCB1 mutations can occur in isolation. SMARCB1 mutated tumors are associated with overactivation of the MEK pathway, which may explain tumor response to selumetinib. This case highlights the potential for targeted therapies in NF2-associated tumors. Additionally, the partial response suggests increased CNS penetration of selumetinib locally at the site of the tumor. To the best of our knowledge, this is the first reported case for using selumetinib in NF2-associated tumors or ependymomas.