Safety of emapalumab in pediatric patients with primary hemophagocytic lymphohistiocytosis: findings from the primary analysis of the pivotal phase 2/3 study.

Primary hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening, immune regulatory disorder characterized by a hyperinflammatory state in which patients typically develop fever, splenomegaly, cytopenias and coagulopathy. In patients with primary HLH, the cytokine Interferon gamma (IFNy) is often markedly elevated and is considered a key contributor to the hyperinflammatory state. The treatment goal of primary HLH is to stabilize the disease by controlling the associated hyperinflammation in order to bring patients to transplantation, the only curative therapy. Current conventional therapy for HLH comprises immunochemotherapies, which are associated with opportunistic infections, toxicity, and high morbidity and mortality. Emapalumab is a fully human, anti-IFNy monoclonal antibody that neutralizes IFNy. It is approved by the FDA for the treatment of adult and pediatric patients with primary HLH with refractory, recurrent or progressive disease, or intolerance with conventional HLH therapy. Herein, we report on the safety of emapalumab in primary HLH seen in the pivotal phase 2/3 study and investigate the relationship of adverse events (AE) to dose and duration of treatment.