title: Vemurafenib in combination with cobimetinib in relapsed and refractory extramedullary multiple myeloma harboring the BRAF V600E mutation.
abstract: BRAF mutations are present in a variety of cancers and cause constitutive activation of the Ras-Raf-MEK-ERK signaling pathway. In cutaneous malignant melanoma, combined treatment with BRAF and MEK inhibitors is associated with high response rates and has been shown to improve progression free as well as overall survival compared to BRAF inhibition alone. In multiple myeloma, BRAF mutations are detectable only in a minority of patients. Only few data are available regarding the clinical activity of BRAF inhibitors in BRAF-positive multiple myeloma patients, including some anecdotal reports on remarkable responses in individuals being resistant to all other available anti-myeloma treatment approaches. We here present the first report on the combination of vemurafenib and cobimetinib in a young patient with highly resistant and rapidly progressing multiple myeloma harboring the BRAF V600E mutation who achieved a rapid and sustained response to this combination therapy.
authors.affiliation: Medical Oncology and Hematology, Kantonsspital Graubuenden, Chur, Switzerland.
authors.forename: Ulrich J M
authors.initials: UJM
authors.lastname: Mey
authors.affiliation: Oncology Centre Hirslanden & Zurich, Zurich, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Renner
authors.affiliation: Medical Oncology and Hematology, Kantonsspital Graubuenden, Chur, Switzerland.
authors.forename: Roger
authors.initials: R
authors.lastname: von Moos
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001384:Azetidines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D009154:Mutation; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000077484:Vemurafenib
chemical_list: D001384:Azetidines; D007211:Indoles; D010880:Piperidines; D013449:Sulfonamides; D000077484:Vemurafenib; D048493:Proto-Oncogene Proteins B-raf; C574276:cobimetinib
keywords: BRAF V600E; cobimetinib; multiple myeloma; vemurafenib