Long-Term Treatment With Emapalumab in an Adult Patient With Refractory Hemophagocytic Lymphohistiocytosis and Systemic Lupus Erythematosus: A Case Report.

Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome characterized by excessive immune activation due to persistently activated cytotoxic lymphocytes and macrophages. HLH can lead to multiorgan dysfunction and can be fatal if left untreated. HLH secondary to autoimmune diseases is referred to as macrophage activation syndrome (MAS). Case Presentation: A female Arab Saudi patient in her late 20s with a history of systemic lupus erythematosus (SLE) presented with reduced oral intake, abdominal pain, decreased urine output, tachypnea, shortness of breath, and acute heart failure. MAS secondary to SLE and associated stress cardiomyopathy was suspected. Despite initial treatment with the HLH-94 protocol, the patient showed no improvement and developed Gram-negative septicemia with worsened cytopenia. Emapalumab, a monoclonal antibody that targets interferon gamma (IFN-γ), was introduced as a salvage therapy, resulting in rapid clinical and biochemical improvement, including normalization of cardiac function. The patient received emapalumab for around 17 months, with good tolerability apart from a brief period of CMV reactivation, achieving sustained remission. Following discontinuation, HLH recurred in the context of newly diagnosed myelodysplastic syndrome and was refractory to conventional therapy but responded again to emapalumab retreatment. At the time of last follow-up, the patient remained clinically stable with no evidence of active HLH while continuing emapalumab therapy in the context of ongoing treatment for her underlying conditions. Conclusions: This case report highlights the potential of emapalumab as an effective therapeutic option for the treatment of relapsed/refractory HLH in adults, including in SLE- and malignancy-associated disease not responding to conventional therapy. It supports its role in achieving rapid disease control, enabling prolonged remission with extended use, and allowing successful retreatment in recurrent HLH, including in high-risk settings with poor outcomes such as malignancy-associated HLH.