Extreme elevation of acute phase reactants and shock secondary to dabrafenib-trametinib

The emerging role of BRAF and MEK tyrosine-kinase inhibitors has shown new opportunities of treatment for patients with advanced melanoma and BRAF mutations. Its use is associated with some toxicities, as pyrexia, that clinicians may not be familiarized with. We present the case of a patient diagnosed with stage IV melanoma BRAF Val600E mutated who was started on dabrafenib and trametinib and developed three severe episodes of fever, hypotension and acute phase reactants elevation during the first 3 months of therapy, in the absence of microbiological demonstration of infection. The episodes were initially managed as a septic shock with broad-spectrum antibiotics and vasoactive drugs, while treatment with dabrafenib and trametinib was withheld. After two subsequent dose reduction of dabrafenib, the patient did not experience new episodes of fever.

Automated summary

The emerging role of BRAF and MEK tyrosine-kinase inhibitors provides new treatment opportunities for patients with advanced melanoma and BRAF mutations, but may be associated with toxicities. This case report describes a patient who developed multiple episodes of fever, hypotension, and acute phase reactants elevation while on dabrafenib and trametinib therapy, initially managed as septic shock without evidence of infection. After dose reduction of dabrafenib, the fever episodes resolved.