Two cases of advanced melanoma with BRAF L597 mutation: Options for systemic treatment.

The combination of BRAF and MEK kinase inhibitors is a well-established treatment for BRAF V600-mutated advanced melanoma. However, the efficacy of these therapies against less common BRAF mutations, such as BRAF L597, remains unclear. We report two cases of advanced melanoma harboring the BRAF L597 mutation. In the first case, a 77-year-old man with metastatic melanoma achieved complete remission following combination therapy with nivolumab and ipilimumab. In the second case, a 50-year-old woman with metastatic melanoma exhibited resistance to multiple systemic therapies, including nivolumab, ipilimumab, and targeted therapy with encorafenib and binimetinib. These cases highlight the variable therapeutic responses in melanoma with the BRAF L597 mutation, suggesting that immune checkpoint inhibitors may be a viable first-line treatment, particularly for patients with a high tumor mutational burden. Further studies are needed to establish optimal treatment strategies for this rare mutation.