Case report of selumetinib as a novel therapy in a neurofibromatosis type 2-associated ependymoma

Abstract

We report partial response (PR) to novel therapy with selumetinib in a patient with Neurofibromatosis type 2 (NF2). A 25-year-old male presented with bilateral vestibular schwannomas, spinal cord intramedullary ependymomas, cranial and spinal meningiomas, spinal nerve root mixed schwannoma-neurofibromas, and peripheral nerve sheath tumors. He tested negative for germline NF2, SWItch/Sucrose Non-Fermentable-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1), and leucine zipper like transcription regulator 1 (LZTR1) mutations. Molecular analysis of a resected cervical spine schwannoma-neurofibroma demonstrated an isolated somatic SMARCB1 mutation. Due to progression of all 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 everolimus toxicity. Three months of treatment resulted in PR in one spinal ependymoma and stable disease in other tumors. This partial response was quantified by the differences in units of intensity in pre- and post-treatment MR image. To the best of our knowledge, this is the first reported case for using selumetinib in NF2-associated tumors or ependymomas.