Life-threatening Lymphatic Malformation With Somatic Activating NRAS Mutation Successfully Treated With Trametinib: A...

Area of Science:

• Vascular Anomalies
• Genetics
• Oncology

Background:

• Kaposiform lymphangiomatosis (KLA) is a rare, aggressive complex lymphatic anomaly (CLA) with no standard curative therapy.
• Current treatments offer symptomatic relief but lack curative potential.
• Sirolimus is a promising therapy, but genetic drivers can influence treatment response.

Purpose of the Study:

• To present a case of KLA with an NRAS p.Gln61Arg mutation.
• To evaluate the efficacy of targeted therapy in a patient with KLA and a RAS-MAPK pathway mutation.
• To highlight the role of genomic profiling in personalized treatment strategies for KLA.

Main Methods:

• Next-generation sequencing (NGS) for genetic analysis.
• Clinical assessment of patient response to sirolimus and trametinib.
• Case report detailing diagnosis and treatment course.

Main Results:

• A 4-year-old male with KLA and an NRAS p.Gln61Arg mutation was identified.
• Initial sirolimus therapy was suboptimal; subsequent trametinib treatment led to significant clinical improvement, including resolution of effusions.
• No significant short-term adverse effects were observed with trametinib.

Conclusions:

• Genomic profiling is crucial for identifying actionable mutations in KLA.
• Targeted therapy with MEK inhibitors like trametinib shows potential for treating KLA with activating NRAS variants.
• Further research is needed to validate trametinib's efficacy and expand targeted therapeutic approaches for vascular anomalies.