Selumetinib Halts Progression of Orbital/Periorbital Plexiform Neurofibromas in Neurofibromatosis Type 1
Ruben Jauregui1, Mekka Garcia2, Aarushi Jain1, Devorah Segal2
1Neurology, NYU Grossman School of Medicine, 2NYU Grossman School of Medicine
Objective:
To describe the treatment response with the MEK inhibitor, selumetinib, in neurofibromatosis type 1 (NF1) patients with orbital/periorbital plexiform neurofibromas (OPPNs).
Background:
NF1 is a multi-system autosomal dominant disorder caused by pathogenic variants in NF1.1 The neuro-ophthalmologic manifestations of NF1 include OPPNs, which are complex optic nerve sheath tumors that can lead to neurologic deficits and vision loss.1,2 Therapeutic management for growing OPPNs may include debulking surgery, although success may be limited by widespread involvement of the lesion.2 Medical management with chemotherapy has not shown benefit, but there have been reports of selumetinib reducing the burden of spinal neurofibromas and OPPNs.3,4
Design/Methods:
Prospective study of three patients with NF1-associated OPPNs. Dosage of selumetinib was based on body-surface area. Once started on selumetinib, patients received monitoring with MRI brain/orbit every 3 months.
Results:
Patient 1 started selumetinib at the age of 4 for a left OPPN. The initial dose of 20mg/10mg was weight-adjusted 6 months later to 20mg b.i.d. The OPPN has remained stable for 26 months after selumetinib initiation. Patient 2 started selumetinib at 20mg b.i.d. at the age of 3 for a left OPPN. This had remained stable in size on MRI 5 months later. Patient 3 started selumetinib at 40mg b.i.d. at the age of 15 for a right OPPN. The lesion remained stable on MRI for the initial 10 months, but increased in size 6 months later. Despite radiographical findings, patient reported subjective improvement on therapy, reporting increase ability to open her eye.
Conclusions:
Selumetinib may represent an important treatment modality in stabilizing lesion size in OPPNs. Additional studies with larger cohort size and longer follow-up are needed to further elucidate disease course on patients taking selumetinib and to evaluate for long-term adverse effects.