Langerhans cell histiocytosis with BRAF p.N486_P490del or MAP2K1 p.K57_G61del treated by the MEK inhibitor trametinib

Pediatr Blood Cancer. 2020 Dec;67(12):e28712. doi: 10.1002/pbc.28712. Epub 2020 Sep 29.

Abstract

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.

Keywords: Langerhans cell histiocytosis; MAPK pathway variants; trametinib.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Agents / therapeutic use*
  • Gene Deletion*
  • Histiocytosis, Langerhans-Cell / drug therapy*
  • Histiocytosis, Langerhans-Cell / genetics
  • Histiocytosis, Langerhans-Cell / pathology
  • Humans
  • MAP Kinase Kinase 1 / antagonists & inhibitors*
  • Male
  • Mutation*
  • Prognosis
  • Proto-Oncogene Proteins B-raf / genetics*
  • Pyridones / therapeutic use*
  • Pyrimidinones / therapeutic use*
  • Young Adult

Substances

  • Antineoplastic Agents
  • Pyridones
  • Pyrimidinones
  • trametinib
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • MAP Kinase Kinase 1