RARE-07. THE EFFECT OF SELUMETINIB ON SPINAL NEUROFIBROMAS IN PATIENTS WITH NF1

Abstract

BACKGROUND: Spinal neurofibromas (SNF) in neurofibromatosis type 1 (NF1) can cause progressive cord compression with associated morbidity. A phase 1 study of the MEK inhibitor Selumetinib in patients with plexiform neurofibromas (PN) demonstrated PN shrinkage and improvement clinical symptoms. Here we describe the effect of selumetinib on SNF burden. METHODS: Participants of the ongoing phase 2 pediatric (NCT01362803) and adult (NCT02407405) selumetinib studies for NF1 PN, who underwent serial spine MRI exams were examined. The effect of selumetinib on the size of SNF, shape of the spinal canal, spinal cord, and cerebrospinal fluid (CSF) space were evaluated at baseline and during treatment by linear measurements. RESULTS: Nineteen patients (14 male), median age 15.5 years (range, 6–60) had documented SNF and were included in the analysis. Six patients had prior spinal decompression surgery and all had SNF extending into the central canal at one or more levels (14 cervical, 2 thoracic, 12 lumbosacral). Deformation of the spinal cord cross-section was observed in 17 patients. Sixteen patients completed at least 12 cycles of treatment, and 3 received 8 cycles. Tumors remained stable in 5 patients, improvement was observed in 14 patients (9 children, 5 adults) and no SNFs exhibited progression during treatment. Most improvements were observed after 4 cycles and were maintained. The most notable change was expansion of the CSF space (due to tumor shrinkage), with CSF signal becoming circumferential. Analysis of clinical correlations is ongoing. CONCLUSIONS: This is the first study assessing selumetinib effect on SNF. In 14 of 19 patients with SNF, we observed prolonged improvement in SNF attributes. Our findings indicate selumetinib may prevent worsening of cord compression, and reduce surgical interventions. The role of MEK inhibitor therapy for the treatment of SNF needs to be prospectively evaluated along with functional measures and patient reported outcomes.