Case ReportVemurafenib Response in 2 Patients With Posttransplant Refractory BRAF V600E–Mutated Multiple Myeloma
Introduction
BRAF (v-raf murine sarcoma viral oncogene homolog B) V600E activating mutations have been observed in melanoma, non–small-cell lung cancer, colorectal carcinoma, and a wide variety of additional malignancies, yet only some of these diseases have been tested for responses to BRAF V600E–specific inhibitors.1, 2 BRAF V600E and other less potent activating BRAF alterations have also been described in multiple myeloma3; however, the clinical response to BRAF-targeted therapy for BRAF V600E–mutated multiple myeloma is largely unknown. This report presents 2 posttransplant/conventional therapy–resistant patients with multiple myeloma with BRAF V600E mutations that were identified by a clinical next-generation sequencing–based assay and were subsequently treated with vemurafenib.
Section snippets
Patient 1
A 65-year-old man presented with a 5-cm palpable skull lesion. Serum protein electrophoresis found a monoclonal immunoglobulin G (IgG) κ spike of 6 g/dL and 324 mg/dL of serum free κ light chains. Diagnostic workup for myeloma included a 24-hour urine collection (which found excretion of 5.2 g of κ light chain), a bone marrow biopsy (which found a diffuse infiltration with plasma cells notable for expression of CD56), normal metaphase cytogenetic analysis, and a normal myeloma fluorescence in
Discussion
Activating genomic alterations in the mitogen-activated protein kinase signaling pathway are the most frequent oncogenic driver mutations in multiple myeloma.3 Whereas mutations in NRAS (neuroblastoma RAS viral (v-ras) oncogene homolog) and KRAS (Kirsten rat sarcoma viral oncogene homolog) may occur in 40% to 50% of myeloma cases, BRAF mutations are less frequent, occurring in approximately 2% to 4% of primary myelomas,4 with the majority of these alterations consisting of BRAF V600E activating
Conclusion
Patients with BRAF V600E–mutated myeloma may have an unusually aggressive clinical course associated with prominent extramedullary disease and a short duration of response to standard therapies. Vemurafenib has clinical activity in this form of multiple myeloma.
Disclosure
J.C., D.M., P.J.S., G.A.P., J.S.R., V.A.M., and S.M.A. are employees of and have equity interest in Foundation Medicine Inc. J.S. and J.P.S. state that they have no conflicts of interest.
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