title: Dramatic efficacy of vemurafenib in both multisystemic and refractory Erdheim-Chester disease and Langerhans cell histiocytosis harboring the BRAF V600E mutation.
abstract: Histiocytoses are rare disorders of unknown origin with highly heterogeneous prognosis. BRAFV600E gain-of-function mutations have been observed in 57% of cases of Langerhans cell histiocytosis (LCH) and 54% of cases of Erdheim-Chester disease (ECD), but not in other types of histiocytoses. Targeted therapy with an inhibitor of mutated BRAF (vemurafenib) improves survival of patients with melanoma. Here, we report vemurafenib treatment of 3 patients with multisystemic and refractory ECD carrying the BRAFV600E mutation; 2 also had skin or lymph node LCH involvement. The patients were assessed clinically, biologically (CRP values), histologically (skin biopsy), and morphologically (positron emission tomography [PET], computed tomography and magnetic resonance imaging). For all patients, vemurafenib treatment led to substantial and rapid clinical and biologic improvement, and the tumor response was confirmed by PET, computed tomography, and/or magnetic resonance imaging 1 month after treatment initiation. For the first patient treated, the PET response increased between months 1 and 4 of treatment. The treatment remained effective after 4 months of follow-up although persistent disease activity was still observed. Treatment with vemurafenib, a newly approved BRAF inhibitor, should be considered for patients with severe and refractory BRAFV600E histiocytoses, particularly when the disease is life-threatening.
authors.affiliation: Department of Internal Medicine and French Reference Center for Rare Auto-immune and Systemic Diseases, Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié-Salpêtrière Hospital, Paris, France. julien.haroche@psl.aphp.fr
authors.forename: Julien
authors.initials: J
authors.lastname: Haroche
authors.forename: Fleur
authors.initials: F
authors.lastname: Cohen-Aubart
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Emile
authors.forename: Laurent
authors.initials: L
authors.lastname: Arnaud
authors.forename: Philippe
authors.initials: P
authors.lastname: Maksud
authors.forename: Frédéric
authors.initials: F
authors.lastname: Charlotte
authors.forename: Philippe
authors.initials: P
authors.lastname: Cluzel
authors.forename: Aurélie
authors.initials: A
authors.lastname: Drier
authors.forename: Baptiste
authors.initials: B
authors.lastname: Hervier
authors.forename: Neïla
authors.initials: N
authors.lastname: Benameur
authors.forename: Sophie
authors.initials: S
authors.lastname: Besnard
authors.forename: Jean
authors.initials: J
authors.lastname: Donadieu
authors.forename: Zahir
authors.initials: Z
authors.lastname: Amoura
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D004351:Drug Resistance / Q000187:drug effects / Q000235:genetics; D031249:Erdheim-Chester Disease / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005260:Female; D018698:Glutamic Acid / Q000235:genetics; D006646:Histiocytosis, Langerhans-Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000502:physiology; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome; D014633:Valine / Q000235:genetics; D000077484:Vemurafenib
chemical_list: D000893:Anti-Inflammatory Agents; D007211:Indoles; D013449:Sulfonamides; D000077484:Vemurafenib; D018698:Glutamic Acid; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D014633:Valine