Dabrafenib and trametinib in Langerhans cell histiocytosis and other histiocytic disorders

Haematologica. 2023 Sep 21. doi: 10.3324/haematol.2023.283295. Online ahead of print.ABSTRACTStandard treatment for Langerhans Cell Histiocytosis (LCH) is chemotherapy, with high failure rates. Since MAP-kinase activating mutations are found in most cases, BRAF- and MEKinhibitors have been used successfully to treat patients with refractory or relapsed disease. However, data on long-term responses in children are limited and no data exist on their use as first-line therapy. We treated thirty-four patients (26 LCH, 2 Juvenile Xanthogranuloma, 2 Rosai-Dorfman Disease, 4 presumed single site-CNS histiocytosis) with either dabrafenib and/or trametinib, either as first line or after relapse or failure of chemotherapy. Sixteen patients aged 1.3-21 years, had disease that was recurrent or refractory to chemotherapy, 9 of whom had multisystem LCH with risk-organ involvement. With a median treatment duration of 4.3 years, 15 (94%) patients have sustained favorable responses. Eighteen patients aged 0.2-45 years received the inhibitor as first-line treatment. All of these have had sustained favorable responses, with a median treatment duration of 2.5 years. Three patients with presumed isolated CNS/pituitary-stalk histiocytosis demonstrated stabilization or improvement of disease. Overall, inhibitors were well tolerated. Five patients with single system LCH discontinued therapy and remain off therapy without recurrence. In contrast, all 4 patients with multisystem disease that discontin...
Source: Haematologica - Category: Hematology Authors: Source Type: research