Dabrafenib plus trametinib in BRAF V600E-mutant Erdheim-Chester disease: a case series including CNS involvement.

BACKGROUND: Erdheim-Chester disease (ECD) is a rare clonal non-Langerhans cell histiocytosis characterized by the infiltration of foamy, CD68-positive/CD1a-negative histiocytes into multiple organ systems. Activating MAPK/ERK pathway mutations, most commonly BRAF V600E, represent common targets for ECD therapies. Although vemurafenib has been approved for BRAF V600E-mutant ECD, data regarding dual BRAF and MEK inhibition remain scarce. METHODS: We recently treated three patients with BRAF V600E-mutant ECD using dabrafenib combined with trametinib. The clinical presentations included skeletal, cardiovascular, retroperitoneal, and central nervous system (CNS) involvement. RESULTS: Two patients achieved clinical and radiologic improvement, including resolution of CNS symptoms. Notably, BRAF V600E immunohistochemical staining was faint, equivocal, or negative in all patients, whereas molecular testing confirmed the mutation. One patient developed grade 3 rhabdomyolysis after one year, requiring dose reduction. The third patient maintained stable disease, with positron emission tomography demonstrating decreased fluorodeoxyglucose uptake that indicated early metabolic improvement. CONCLUSION: This case series highlights the effectiveness and tolerability of dabrafenib plus trametinib for BRAF V600E-mutant ECD, including cases with CNS and cardiovascular involvement. Molecular diagnosis and targeted therapy appear to be critical for optimizing outcomes, although further prospective studies are warranted to clarify the long-term effectiveness, resistance mechanisms, and optimal duration of this treatment approach.