Reproducible and Sustained Efficacy of Targeted Therapy With Vemurafenib in Patients With <i>BRAF^V600E</i>-Mutated Erdheim-Chester Disease

<jats:sec><jats:title>Purpose</jats:title><jats:p> Histiocytoses are rare disorders with heterogeneous prognosis. BRAF<jats:sup>V600E</jats:sup> mutations have been observed in half of patients with Langerhans cell histiocytosis (LCH) and in 50% to 100% of patients with Erdheim-Chester disease (ECD) patients. We recently reported short-term efficacy of a BRAF inhibitor (vemurafenib) in three patients with multisystemic ECD. </jats:p></jats:sec><jats:sec><jats:title>Patients and Methods</jats:title><jats:p> Vemurafenib was given to eight patients with multisystemic ECD with CNS and/or cardiac involvement. All patients were refractory to first-line treatment and harbored a BRAF<jats:sup>V600E</jats:sup> mutation. Four patients also had LCH lesions. Positron emission tomography (PET) scan response at month 6 was used as the main evaluation criterion. Secondary evaluation criteria were comparison at baseline and at last visit of PET and of cardiovascular and cerebral infiltrations (computed tomography scan and magnetic resonance imaging [MRI]). </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> All patients were partial metabolic responders at 6 months of vemurafenib, and the median reduction in maximum standardized uptake value was 63.5% (range, 41.3% to 86.9%). Evaluation of cardiac and aortic infiltrations showed that seven patients had a partial response and one patient had stable disease according to surface measurements derived from RECIST criteria. The four patients with infratentorial CNS infiltration had an objective decrease of the lesions on MRI. All patients had an improvement of general symptoms and a persistent response to vemurafenib, with a median follow-up time of 10.5 months (range, 6 to 16 months). Skin adverse effects were frequent and severe. </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> Vemurafenib has an objective and sustained efficacy in BRAF<jats:sup>V600E</jats:sup>-mutated ECD as second-line therapy. In contrast to melanoma, no resistance has emerged to date after 6 to 16 months. </jats:p></jats:sec>