Efficacy of Emapalumab as Rescue Therapy in a Pediatric Case of Secondary Hemophagocytic Lymphohistiocytosis

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening hyperinflammatory syndrome driven by uncontrolled immune activation and excessive cytokine release, in which interferon-γ (IFN-γ) plays a central pathogenic role. Data regarding targeted IFN-γ blockade in secondary HLH remain limited. We report a case of a previously healthy 17-year-old girl who developed severe secondary HLH, characterized by persistent fever, progressive cytopenia, marked hyperferritinemia, disseminated intravascular coagulation, multiorgan failure, and life-threatening gastrointestinal bleeding. Despite intensive treatment with intravenous immunoglobulin, high-dose corticosteroids, anakinra, cyclosporine, and plasmapheresis, the hyperinflammatory state remained refractory. Emapalumab, a monoclonal antibody targeting IFN-γ, was initiated as rescue therapy in the pediatric intensive care unit, resulting in rapid clinical stabilization and marked laboratory improvement, which allowed tapering of immunosuppressive treatments. Following recovery from the cytokine storm, a splenectomy was safely performed, revealing an underlying anaplastic large cell lymphoma. This case highlights the potential life-saving role of emapalumab as a rescue therapy for refractory secondary HLH and suggests that timely IFN-γ blockade may stabilize critically ill patients and facilitate definitive diagnostic and therapeutic interventions in malignancy-associated HLH.