Lionel Chow, MD, PhD

Panelists discuss the future of NF1-associated plexiform neurofibromas management, highlighting the potential for advances in targeted therapies, gene therapies, and personalized medicine to offer more effective, tailored treatments, while emphasizing early detection, improved imaging, and a greater focus on quality of life through psychosocial support, pain management, and functional rehabilitation.

Panelists discuss the mechanisms of action of gene therapy for NF1-associated plexiform neurofibromas, focusing on restoring functional neurofibromin to regulate the RAS/MAPK pathway and prevent tumor formation, while highlighting promising early clinical trial results showing reduced tumor volume and improved symptoms, alongside the need for further studies to assess long-term safety and efficacy.

Panelists discuss current guidelines recommending mirdametinib for pediatric patients (2 years and older) with progressive, symptomatic NF1-associated plexiform neurofibromas that are inoperable or difficult to manage surgically, and emphasize the importance of early initiation, regular monitoring, and a multidisciplinary approach to optimize treatment outcomes.

Panelists discuss how biomarkers, including genetic testing and tumor profiling, can help identify patients with RAS/MEK/ERK pathway activation or specific NF1 mutations, enabling more personalized and effective treatment with therapies like mirdametinib or gene therapies for progressive, symptomatic NF1-associated plexiform neurofibromas.

Panelists discuss how mirdametinib's oral administration offers convenience and improves compliance, especially in pediatric patients, and how its ability to stabilize progressive, symptomatic NF1-associated plexiform neurofibromas without the need for invasive procedures fills a critical gap in treatment options while also addressing potential access barriers related to insurance coverage and cost.

Panelists discuss the promising results of the ReNeu trial for mirdametinib, highlighting its significant tumor shrinkage and improvements in quality of life for patients with NF1-associated plexiform neurofibromas, and how mirdametinib’s favorable adverse effect profile and effectiveness in complex or refractory cases may provide a valuable treatment option in real-world clinical practice.

Panelists discuss key lessons learned from previous NF1-associated plexiform neurofibroma therapies, including the limitations of traditional treatments due to high toxicity and limited efficacy, and how these challenges are driving the development of more targeted therapies like MEK inhibitors, personalized medicine, and combination strategies to improve outcomes and reduce relapse.

Panelists discuss the critical role of psychosocial support in managing NF1-associated plexiform neurofibromas, emphasizing the need for psychotherapy, counseling, and social work interventions to address anxiety, depression, and social stigma while also highlighting challenges in accessing therapies like selumetinib due to cost, insurance barriers, and health care system disparities.

Panelists discuss the exploration of combination therapies in treating complex or refractory NF1-associated plexiform neurofibromas, including MEK inhibitors combined with PI3K inhibitors, anti-angiogenic agents, and chemotherapies, and review early clinical findings suggesting potential synergistic effects, while highlighting concerns about toxicity and the need for careful patient monitoring.

Panelists discuss key findings supporting the use of MEK inhibitors, such as selumetinib, in treating NF1-associated plexiform neurofibromas, emphasizing its impact on clinical decision-making, particularly for pediatric patients with progressive, symptomatic tumors who are not surgical candidates, and review current guidelines recommending its use to control tumor growth and improve quality of life.

Panelists discuss how MEK inhibitors, such as trametinib and selumetinib, are emerging as first-line treatments for symptomatic NF1-associated plexiform neurofibromas, especially in progressive or inoperable cases, while emphasizing the importance of surgical resection, pain management, physical therapy, and psychosocial support for improving quality of life.

Panelists discuss the current management goals for NF1-associated plexiform neurofibromas, focusing on tumor control, symptom management, and prevention of malignant transformation, while highlighting the evolving future goals of targeted therapies, personalized treatment plans, and enhanced early detection to improve outcomes.

Panelists discuss the unmet needs in NF1-associated plexiform neurofibromas, highlighting gaps in effective treatment, pain management, psychosocial support, and prevention of malignant transformation, while emphasizing the importance of early intervention, multidisciplinary care, and ongoing research into targeted therapies and improved surveillance protocols.

Panelists discuss how severe symptoms in NF1-associated plexiform neurofibromas are influenced by tumor size, location, growth rate, and genetic factors, and emphasize the importance of early intervention, regular imaging, and a multidisciplinary approach for monitoring and managing risks, including malignant transformation and complications.

Panelists discuss how NF1-associated plexiform neurofibromas can cause significant morbidity, including disfigurement, pain, and neurologic impairment, with the risk of malignant transformation, and emphasize the impact of these tumors on quality of life, daily functioning, and prognosis based on tumor characteristics and access to care.

Panelists discuss how plexiform neurofibromas in NF1 often emerge in early childhood with progressive growth and symptoms such as disfigurement, pain, and neurologic deficits, noting that rapid enlargement may indicate malignant transformation, and that presentation and complications differ between pediatric and adult patients.

Panelists discuss how neurofibromatosis type 1 (NF1) is typically diagnosed in early childhood using National Institutes of Health (NIH) clinical criteria, with genetic testing supporting unclear cases, and highlight the global prevalence of NF1 and the high incidence of plexiform neurofibromas, which affect up to 50% of patients regardless of racial or geographic background.

Panelists discuss how mutations in the NF1 gene lead to loss of neurofibromin function, resulting in hyperactivation of the RAS/MAPK and PI3K/AKT/mTOR pathways, and how this molecular dysregulation drives abnormal cell proliferation and tumor development in NF1.