P55-6 Encorafenib for Erdheim-Chester disease harboring the BRAFV600E mutation

Abstract

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis harboring the BRAFV600E mutation in about 50% of patients. Use of BRAF inhibitor for BRAF-mutated ECD was one of the representative practices of precision medicine. FDA approved vemurafenib for BRAF-mutated ECD, and dabrafenib and encorafenib in addition to vemurafenib for BRAF-mutated melanoma. Though there have been some cases reported of use of dabrafenib for BRAF-mutated ECD, there has never been reported of use of encorafenib. Here we report the first treatment of encorafenib for BRAF-mutated ECD, which showed dramatic efficacy. An 81-year-old female was admitted to our hospital because of dyspnea. CT scanning revealed pericardial effusion, and perinephric soft tissue thickening. 99mTc bone scintigraphy showed bilateral symmetric osteosclerosis of bones of the legs. Her respiratory symptom was resolved by aspiration of pericardial effusion. We suspected of ECD based on specific clinical findings and followed up her in the outpatient setting. Two years later, she presented to our hospital because of dyspnea and a headache. FDG-PET/CT revealed pleural effusion in addition to the findings described above. MRI of the head showed a mass compressing the brainstem. Pleural specimens revealed pathological findings of ECD. NGS identified the BRAFV600E mutation. After obtaining the ethics committee approval, she started to receive encorafenib 100mg once daily. After three months, MRI of the head showed a 30% reduction in size of the mass, and FDG-PET/CT revealed partial metabolic response. Adverse events of encorafenib were Grade2 hand-foot syndrome and Grade1 alopecia. Recently, a framework of precision medicine has been actively constructed in Japan. However, genetic testing of BRAF mutation and use of BRAF inhibitor for ECD is not covered by the Japanese insurance system. We hope clinical utility of testing comprehensive target genes and using target drugs is possible for rare diseases in Japan.