Dr Gershon on Ongoing Research Priorities for NF1-Associated Plexiform Neurofibromas

“The needs of patients with neurofibromatosis are large. One of the large unmet needs is an understanding of the neuropsychosocial aspects of neurofibromatosis.”

Timothy R. Gershon, MD, PhD, a professor in the Department of Pediatrics at Emory University School of Medicine, director of the Children's Center for Neurosciences Research, and a member of the Cell and Molecular Biology Research Program at Winship Cancer Institute of Emory University, outlined ongoing research priorities in the management of neurofibromatosis type 1 (NF1)–associated plexiform neurofibromas (PNs).

Treatment options for select patients with NF1-associated PNs grew following the February 2025 FDA approval of mirdametinib (Gomekli). The agent is indicated for adult and pediatric patients 2 years of age and older with NF1 who have symptomatic PNs not amenable to complete resection.

Although mirdametinib provides a significant therapeutic option for those who cannot have their tumors surgically resected, Gershon emphasized that multiple unmet needs remain, particularly in the neuropsychosocial domain. NF1 is associated with an elevated risk of autism spectrum disorder, learning differences, and other cognitive or psychosocial challenges that may necessitate differentiated educational support. Currently, there is no established method for linking NF1 genotypes to specific neuropsychosocial phenotypes, limiting the ability to identify patients most likely to require targeted interventions. Addressing this knowledge gap could enable earlier, more personalized, supportive care.

In addition to optimizing supportive strategies, Gershon noted that surgery continues to be a key modality for PN management; however, the role of MEK inhibitors, such as mirdametinib, in the perioperative setting remains undefined. He highlighted the need to investigate whether adjuvant mirdametinib administration after surgical resection could reduce recurrence risk—an approach not yet formally evaluated in clinical trials.

Beyond sequencing, research is also needed to enhance the depth and uniformity of tumor shrinkage achieved with MEK inhibition. Although mirdametinib monotherapy has demonstrated clinical benefit, variability in depth of response suggests that combination regimens may further improve outcomes, Gershon said. He underscored the importance of evaluating additional agents with synergistic mechanisms in parallel with MEK inhibitors to achieve greater and more consistent tumor reductions.