Disseminated Xanthogranuloma with BRAF Gene Fusion and Profound Response to MEK Inhibitor Therapy (ASH 2023)
Regrettably, following the cessation of Trametinib, the patient's lesions rapidly progressed, and her disease worsened beyond the pre-treatment state. Taking into account the 10% PDL-1 positivity, immunotherapy with Pembrolizumab was commenced, resulting in partial improvement...Consequently, Cobimetinib was discontinued, and a continuously dosed MEK inhibitor, Binimetinib, was cautiously administered at a lower dose to mitigate the risk of cardiotoxicity... To our knowledge, this is the first clinical trial documenting MEK inhibition for a patient with xanthoma disseminatum harboring a BRAF fusion. Seeking to target downstream of BRAF, MEK inhibition demonstrated a dramatic response, with rapid relapse upon cessation, supporting a central oncogenic role for BRAF fusion. Further studies should explore alterations in the RAS-BRAF-ERK pathway in nLCH and consider clinical trials with MEK inhibitors.