Abstract
Langerhans cell histiocytosis (LCH), Erdheim-Chester disease (ECD), and a mixed ECD/LCH phenotype are histiocytic neoplasms harboring BRAFV600E mutations in half or more cases. Intracranial manifestations of these diseases are refractory to conventional treatments and associated with morbidity and mortality. Studies have demonstrated that BRAFV600E-mutated ECD/LCH can be treated with vemurafenib with robust responses although treatment can be limited by toxicities or intolerance. The use of dabrafenib, an alternative BRAF inhibitor, has not been studied for the treatment of ECD and/or LCH. Also, there have been no attempts at treatment with dabrafenib in the setting of vemurafenib intolerance. We retrospectively analyzed 9 patients with BRAFV600E-mutated ECD or ECD/LCH, 7 with involvement of the cerebral hemispheres, posterior fossa, dura, or skullbase treated with dabrafenib. Patients were treated as (1) initial therapy, (2) following failure of chemotherapy or radiation, or (3) following discontinuation of vemurafenib because of toxicity or intolerance. Of the 9 patients, 6 had ECD and 3 had overlap ECD/LCH. 4 patients treated with dabrafenib as initial targeted therapy all had a clinical response, and 3 of 4 had a metabolic response by FDG-PET and/or resolution of cranial lesions by MRI. 5 patients initially treated with vemurafenib changed treatment to dabrafenib for toxicity or intolerance. 2 of these 5 patients with intracranial disease relapsed following cessation of vemurafenib and both recaptured a response with dabrafenib. The remaining 3 of 5 maintained their response to vemurafenib although 2 subsequently stopped treatment for intolerance. Here, we report outcomes of treatment with single-agent dabrafenib for ECD or ECD/LCH harboring the BRAFV600E mutation for which treatment induced or maintained a response in all intracranial lesions. Dabrafenib monotherapy can be considered as initial treatment for BRAFV600E-mutated intracranial histiocytosis or in the setting of vemurafenib intolerance.