Langerhans Cell Histiocytosis with BRAF p.N486_P490del or MAP2K1 p.K57_G61del Treated by the MEK Inhibitor Trametinib

Abstract

Langerhans Cell Histiocytosis (LCH) is characterized by activating variants of the MAPK pathway. 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 MAP2K1 p.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 CPK toxicity.

Pearls and updates: cutaneous signs of systemic malignancy

“…Treatment ranges from observation +/- local ablation in SS-LCH [41] to combination of prednisolone and chemotherapy for MS-LCH [35 ▪▪ ,36,37,42]. Targeted therapies, including BRAF [43] and MEK [44] inhibitors, are being investigated for potential role in treating refractory BRAF V600E or MAP2K1 positive disease, respectfully.…”

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

“…There is, however, mounting evidence in support of MAPK pathway inhibition for patients with BRAF V600E mutations. A recent report outlines rapid and durable response of relapsed, multisystemic LCH with either BRAF p.N486_P490 or MAP2K1 p.K57_G61 deletion to MEK inhibitor trametinib 2 . Two of the three patients achieved nonactive disease, including a 2‐year‐old male with MAP2K1 deletion who, despite reports attributing trametinib resistance to MAP2K1 mutations, 3 continues to thrive.…”