Steroid-Refractory Pembrolizumab-Induced Haemophagocytic Lymphohistiocytosis (HLH) Successfully Treated With...

Immune checkpoint inhibitors (ICIs) are increasingly used in advanced malignancies but can cause rare, severe immune-related adverse events (irAEs). Haemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome infrequently reported with ICIs and often challenging to diagnose. We report a case of a woman in her 60s with stage IV lung adenocarcinoma treated with pembrolizumab-based chemoimmunotherapy who developed recurrent, steroid-refractory immune-related hepatitis and pneumonitis. Twenty-four weeks after starting pembrolizumab, she presented with persistent fever, thrombocytopenia, extreme hyperferritinaemia (ferritin >33,500 µg/L), and progressive multiorgan dysfunction. Despite overlap with other irAEs and infection, a high H-score prompted evaluation for HLH, confirmed on bone marrow biopsy with haemophagocytosis. She did not respond to high-dose corticosteroids but showed rapid clinical and biochemical improvement following treatment with the interleukin-1 receptor antagonist anakinra, including resolution of respiratory failure, normalisation of liver enzymes, and recovery of cytopenias. Pembrolizumab was permanently discontinued. This case emphasises the importance of considering HLH in patients receiving ICIs who develop unexplained hyperinflammation and cytopenias and highlights the emerging role of targeted immunomodulatory therapy in steroid-refractory cases. Steroid-refractory pembrolizumab-induced HLH can respond rapidly to anakinra, with early interleukin-1 blockade potentially improving outcomes while avoiding cytotoxic therapy. Early recognition and prompt intervention are critical to reducing morbidity and mortality in this rare but potentially fatal complication of immunotherapy.