Single-agent dabrafenib for BRAF V600E -mutated histiocytosis

Single-agent dabrafenib for BRAF V600E-mutated histiocytosisLangerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD) are clonal disorders of the monocyte/macrophage and dendritic cell lineages characterized by infiltration of histiocytes, acute and chronic inflammation, and fibrosis that can involve multiple organ systems and cause a wide range of clinical manifestations.Even though LCH and ECD are clinically and pathologically distinct, both harbor BRAF V600E mutations in ~50% of cases, 1 and nearly 20% of patients with ECD have a diagnosis of both ECD and LCH simultaneously [mixed histiocytosis (MH)]. 2 Several retrospective cases and one prospective clinical trial have demonstrated that BRAF V600E -mutated ECD/LCH can be treated with vemurafenib with responses that are robust and durable.[3][4][5] Vemurafenib recently obtained approval by the Food and Drug administration for treatment of BRAF V600E -mutated ECD on the basis of the VE-BASKET trial.6 However, many patients require dose reductions of vemurafenib, or discontinuation, due to toxicity.3,4 While there are no direct comparisons of vemurafenib to dabrafenib, several studies report a lower incidence of adverse events with dabrafenib.7,8 There have been three single cases reported of treatment of BRAF V600E -mutated ECD 9,10 with dabrafenib, an alternative BRAF inhibitor approved for treatment of BRAF V600E -mutant metastatic melanoma.However, thus far there have been no LCH patients treated with dabrafenib, and there has been only one report of treatment with dabrafenib in the setting of vemurafenib intolerance.11 Herein, we report a series of 11 patients, from three institutions, with ECD or ECD/LCH treated with single agent dabrafenib as (1) initial histiocytosis therapy, (2) following failure of chemotherapy or radiation, or (3) following discontinuation of vemurafenib therapy because of toxicity or intolerance.This is a retrospective study of patients with ECD or ECD/LCH treated between January 1 st , 2014 and October 31 st , 2017, at the Memorial Sloan Kettering Cancer Center (MSKCC), NY, USA, the Department of Hematology at Shaare Zedek Medical Center in Jerusalem, Israel, and the University of Florida Health Cancer Center at Orlando Health, FL, USA.This retrospective review was approved with a waiver of consent by the Institutional Review Board.ECD was diagnosed based on criteria which has been previously published, 12 and in all cases tissue biopsy demonstrated CD68 + /CD1a -histiocytic infiltration in the haematologica 2018; 103:e177 CASE REPORTS *Indicates dabrafenib as first targeted therapy. 1 Erdheim-Chester Disease (ECD). 2 Langerhans Cell Histiocytosis (LCH).3 Partial Metabolic Response (PMR).4 Interferon-a (IFN-a).5 Complete Metabolic Response (CMR).FDG-PET/CT: 18-fluorodeoxyglucose positron emission tomographic/computed tomography; BID: twice a day.