Langerhans cell histiocytosis with BRAF p.N486_P490del or MAP2K1 p.K57_G61del treated by the MEK inhibitor trametinib.
Yoav H MessingerBruce C BostromDamon R OlsonNathan P GossaiLane H MillerMichael K RichardsPublished in: Pediatric blood & cancer (2020)
Activating variants of the MAPK pathway have been found in some Langerhans cell histiocytosis (LCH) lesions. Inhibition of the MAPK pathway with trametinib (MEK inhibitor) has been shown to induce responses in LCH patients. Two adolescent males with LCH driven by BRAF p.N486_P490del have received trametinib for >1 year with no reactivation in one and partial response in another (including stable lung disease). A third male with neonatal LCH and MAP2K1p.K57_G61del had a complete response to trametinib with no active disease after 22 months. All patients continue on trametinib monotherapy with tolerable skin and creatine phosphokinase toxicity.
Keyphrases
- end stage renal disease
- newly diagnosed
- signaling pathway
- ejection fraction
- chronic kidney disease
- oxidative stress
- prognostic factors
- pi k akt
- cell therapy
- single cell
- young adults
- mental health
- patient reported outcomes
- randomized controlled trial
- gene expression
- mesenchymal stem cells
- cell proliferation
- soft tissue
- open label
- high density