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NF1-Associated Tumors FAQs
NF1-Associated Tumors and MEK Inhibitors: Answers to Your Questions

Released: January 24, 2025

Expiration: January 23, 2026

Jaishri Blakeley
Jaishri Blakeley, MD
Miriam Bornhorst
Miriam Bornhorst, MD
Michael J. Fisher
Michael J. Fisher, MD
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Key Takeaways
  • Biopsy is rarely required for the diagnosis of NF1-associated optic pathway glioma in children.
  • Selumetinib has evidence for use in adults with plexiform neurofibromas who need a systemic therapy approach.

In this commentary, Jaishri Blakeley, MD; Miriam Bornhorst, MD; and Michael J Fisher, MD, address clinical questions asked by the audience during the recent symposium titled, “Precision Therapeutics for NF1-Associated Tumors: Improved Outcomes Through Targeted MEK Inhibition” held during the 2024 Society for Neuro-Oncology (SNO) Annual Meeting in Houston. NF1 is an autosomal dominant neurocutaneous genetic syndrome resulting in altered or absent neurofibromin expression that can affect multiple different organs or regions of the body and predispose individuals to tumor development. As of early January 2025, selumetinib is the only approved MEK inhibitor in this setting with an indication for pediatric patients aged 2 years or older with NF1 who have symptomatic, inoperable plexiform neurofibromas. A second MEK inhibitor, mirdametinib, is currently under FDA priority review for the treatment of adults and children with NF1-associated plexiform neurofibromas.

Do you require a biopsy for an optic pathway glioma (OPG) diagnosis or do you accept the MRI diagnosis?

Michael J Fisher, MD: So, not just in patients with OPGs, but in general in children with NF1, I am using the MRI scan to make the diagnosis of low-grade glioma, looking for mass effect or enhancement. Usually, one of the big challenges in children with NF1 is that there are often focal areas of T2 signal hyperintensity, which at one point were called unidentified bright objects or spongiform changes and are now called focal areas of signal intensity (FASIs). I think that these FASIs occur in almost all children with NF1, if you happen to scan them at the right time, and then disappear over time in many patients. It is not possible to tell whether an identified FASI is going to be an early glioma or not. Because of the observation that in most of the children who develop low-grade gliomas the tumor never progresses, never causes problems, and never needs treatment, we do not recommend a biopsy to diagnose them even if you are planning to start treatment. However, if there is something atypical about the presentation such as a rapidly growing tumor, evidence of peritumor edema, or acute onset of neurologic symptoms, a biopsy might be useful.

How does one diagnose adult NF1-associated high-grade glioma? Does the occurrence of any NF1 mutation suffice?

Jaishri Blakeley, MD: Diagnosing an adult with an NF1-associated glioma first requires that the adult patient must have the NF1 germline mutation. Second, there must be a mass on the brain MRI; however, we do not screen for this in adulthood. Typically, pediatric patients with NF1-associated high-grade glioma present with a tumor outside of the optic pathway, a classic OPG. Gliomas that occur just outside the optic pathway in pediatric patients may require additional subsequent MRIs to follow these patients into adulthood. Most of the time, NF1-associated high-grade gliomas in adults present as an individual with NF1 who has a new symptom. In this case, you don't need to do a tissue biopsy to determine if it is an NF1-associated glioma. However, you do need the tissue to see what other gene alterations there are as this will help to better characterize their prognosis. A converse situation is you have an adult who does not have a germline NF1 mutation. They instead have a sporadic glioma; approximately 20% of sporadic gliomas have a somatic NF1 loss. In this scenario, you confirm that the person does not have a germline NF1 mutation and they have had next-generation sequencing or another test that shows that they have an NF1 loss, and thus a sporadic NF1-altered glioma. 

Has a reason for nonresponse of plexiform neurofibromas to MEK inhibitor treatment been identified?

Miriam Bornhorst, MD: The answer is no. Usually biopsies and tissue are not obtained with NF1-associated plexiform neurofibromas as is true with the OPGs or low-grade gliomas. Therefore, we haven't really been able to assess why some patients with plexiform neurofibromas do not respond very well to systemic treatment with a MEK inhibitor. Of course, there are other factors such as compliance; however, there are still many unanswered questions with plexiform neurofibromas. 

Is there any evidence to support selumetinib use in adults with NF1-associated tumors?

Miriam Bornhorst, MD: Selumetinib does appear to be effective for adults with plexiform neurofibromas based on preliminary data from a phase II trial that showed a partial response in 16 of 26 patients (61.5%). In addition, a recent press release on the double-blind, placebo-controlled phase III KOMET trial of selumetinib in adults with symptomatic, inoperable NF1-associated plexiform neurofibromas indicated that the trial met its primary endpoint of improved overall response rate. We await the presentation of these data. The primary problem associated with the use of selumetinib in this setting right now is that it is not yet FDA approved for adults. So even though we know that it works and we do use it in the clinic for adults with NF1-plexiform neurofibromas, there are barriers to access. In fact, it generally takes me about a day to get approval and it can take others a little bit longer.

Do you treat MEK inhibitor–related rash prophylactically using doxycycline or something else?

Jaishri Blakeley, MD: Very early on, I usually start with something like oral doxycycline or minocycline. Week 1 of treatment with a MEK inhibitor, I usually also prescribe topical clindamycin, and then I counsel them about how hot their shower or bath can be and the importance of wearing sunblock. If healthcare professionals and patients do these steps upfront, we can manage MEK inhibitor–related rash well. Unfortunately, there are no strategies to prevent paronychia, unlike the strategies available for acneiform rash. Epsom salt soaks can be helpful when paronychia first appears. Another potential MEK inhibitor–related skin adverse event is seborrheic dermatitis: very tight, itchy, and dry skin. With seborrheic dermatitis, patients can try medicated dandruff shampoos. If the seborrheic dermatitis is starting to feel thicker and with some thickening of the scalp, then you can prescribe a ketoconazole shampoo. 

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