Uncommon BRAF Mutations Associated with Durable Responseto Immunotherapy in Patients with Metastatic Melanoma

Melanoma is a disease process which has been increasing in incidence over the past three decades and metastatic melanoma carriesa poor prognosis. Through genetic studies of this disease, it has been determined that the BRAF V600 mutation plays a majorrole in the pathophysiology of the disease and this has led to the utilization of targeted therapy (BRAF and MEK inhibitors)in its treatment. Other BRAF mutations (non-V600 mutations) are rare in melanoma and targeted therapy is not indicated forpatients with these mutations due to reduced response rates. An emerging option for metastatic melanoma with uncommon BRAFmutations is immunotherapy using checkpoint inhibitors such as PD-1 inhibitors or CTLA-4 inhibitors. Currently, it is unknownhow patients with BRAF non-V600 mutations respond to immunotherapy. This report will examine the effect of immunotherapyon two distinct metastatic melanoma patients, each with uncommon BRAF mutations, occurring outside the V600 locus (E586Kand G469E). These patients were noted to have a durable, complete response when treated with immunotherapy and continue toexhibit a response 9 and 15 months after discontinuing therapy. Further research and clinical trials are needed to study patients withuncommon BRAF mutations and the potential therapeutic benefit of immunotherapy