Long-term Outcome After Vemurafenib / BRAF Inhibitors Interruption in Erdheim-chester Disease

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis. Diagnosis of ECD is based on clinical symptoms, imaging and histology with infiltration of tissues by foamy CD68 positive CD1a negative histiocytes. Because half of the ECD patients carry a BRAFV600E mutation, we recently proposed vemurafenib, an inhibitor of mutant BRAF, as a possible targeted therapy. We have treated more than10 patients with refractory ECD with life-threatening manifestations associated with the BRAFV600E mutation and observed a short and long term efficacy. However, vemurafenib may have several side effects and long term administration of this drug has not been evaluated. In other diseases such as melanoma, duration of administration is usually shorter, due to bad prognosis of the disease and progression despite treatment. As in long-term follow-up, ECD patients with vemurafenib seem to have a stable disease, we want to evaluate the possibility of treatment interruption as this is what we do in our current practice. Other BRAF inhibitors, such as dabrafenib, have recently been proposed for treating BRAF mutated histiocytoses. Other BRAF inhibitor interruption treatment should also be prospectively evaluated.