Real-Life Efficacy and Safety of BRAF Inhibitors in Erdheim-Chester Disease

Erdheim-Chester disease (ECD) is a rare myeloid neoplasm driven by somatic mutations in genes of the MAPK pathway. he BRAF V600E mutation is found in ~60% of ECD patients and can be targeted by specific inhibitors (BRAFi), such as vemurafenib, dabrafenib, and encorafenib. The introduction in 2013 of BRAFi—and more recently of MEK inhibitors (MEKi)—revolutionized the management of patients with ECD. These treatments induce rapid and sustained responses, but relapses occur in most cases upon discontinuation, which is usually prompted by their toxicity. In a recent report on 64 ECD patients treated with BRAFi, discontinuations were very frequent (61%) and mostly induced by adverse events, with poor health-related quality of life and high symptom burden. In contrast, our routine clinical experience suggests a more favorable tolerability profile, with fewer discontinuations and generally manageable toxicities. We herein investigated the real-life efficacy and tolerability of BRAFi monotherapy in a large cohort of patients with ECD.