Successful rechallenge of BRAF/MEK inhibitor with ruxolitinib in BRAF/MEK inhibitor-induced hemophagocytic lymphohistiocytosis like hyperinflammatory syndrome in BRAF V600E-mutated lung adenocarcinoma: a case report

Dabrafenib and trametinib are highly efficacious therapies in patients with BRAF V600E-mutated lung adenocarcinoma (LUAD), but they are occasionally associated with the development of hemophagocytic lymphohistiocytosis (HLH). Here, we describe the first reported case of metastatic BRAF V600E-mutated lung adenocarcinoma that responded to dabrafenib and trametinib, and subsequently developed treatment-associated HLH-like hyperinflammatory syndrome. With the clinical symptoms and inflammatory markers not being adequately controlled with corticosteroids, the patient ultimately required ruxolitinib for the management of HLH-like hyperinflammatory syndrome while still being maintained on dabrafenib and trametinib for LUAD, achieving sustained disease control for both HLH-like hyperinflammatory syndrome and LUAD. This case illustrates HLH as an uncommon but serious immune-mediated toxicity of BRAF/MEK inhibitors, and co-administration of ruxolitinib as a potentially safe and effective therapy in managing HLH-like hyperinflammatory syndrome triggered by BRAF/MEK inhibitors.