Publication date: May 10, 2019
Although the treatment of metastatic melanoma has been significantly improved by both anti-BRAF/MEK and checkpoint immunotherapies, resistance to these treatment modalities remains a substantial clinical problem. Multiple clinical studies are addressing the optimal sequencing of these agents in larger patient cohorts, but successful long-term individualized treatment will likely require the elucidation of resistance mechanisms from post-progression samples. Here, we describe a patient with BRAF-V600E-positive metastatic melanoma who was sequentially treated with BRAF/MEK inhibitors (dabrafenib/trametinib) and checkpoint inhibitor immunotherapy (nivolumab, followed by pembrolizumab). After the emergence of resistance, whole exome sequencing was performed, implicating MAP2K2 and B2M mutations in loss of response to anti-BRAF/MEK and anti-PD1 therapies, respectively.
Richmond, C.S., Vallatharasu, Y., Deviley, J.A., Vos, C.R., Parsons, B.M., and Kenny, P.A. Sequential treatment failures in response to BRAF/MEK and immune checkpoint inhibitors mediated by MAP2K2 and B2M mutations in melanoma. 22606. 2019 Exp Mol Pathol.
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