Discordant Response to Nivolumab Plus Ipilimumab and Identification of BRAF V600E Mutation in Biphasic Malignant Pleural Mesothelioma: Case Report

Therapeutic advancement for malignant pleural mesothelioma (MPM) has been limited. Combination immunotherapy with nivolumab plus ipilimumab is a frontline treatment option for advanced MPM that is typically deployed for patients with sarcomatoid or biphasic MPM. Here, we present a case of biphasic MPM that exhibited a unique response pattern to first-line treatment with nivolumab plus ipilimumab, with brisk response in pleural and mediastinal sites of disease, but rapid progression in osseous/soft tissue sites of disease complicated by pathologic spinal cord compression. Pathologic findings from bony metastasis at progression found pure epithelioid histology without any evidence of sarcomatoid differentiation. Next-generation sequencing of this specimen revealed a <i>BRAF</i> V600E mutation, and the patient was subsequently treated with dabrafenib plus trametinib, achieving ongoing clinical and imaging response in all sites of the disease, including bones. This case supports the use of next-generation sequencing profiling in MPM, particularly in circumstances in which novel discordant response patterns are observed.