Emapalumab for adult and pediatric patients with hemophagocytic lymphohistiocytosis

Introduction Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening hyperinflammatory syndrome. Standard treatment is based on immunosuppressive, cytotoxic drugs and hematopoietic stem cell transplantation (HSCT) in primary HLH. Interferon-gamma (IFN-gamma) plays a key pathogenic role. Emapalumab, a monoclonal antibody directed against IFN-gamma, is the first target therapy approved for primary HLH with refractory, recurrent or progressive disease or intolerance to conventional therapy. Areas covered We reviewed the pharmacological characteristics, safety, efficacy and clinical uses of emapalumab. We summarized the results of current standard treatment based on chemo-immunosuppressive protocols and outlined the alternative options available. Expert opinion Emapalumab is an effective treatment for HLH with a good safety profile. Its efficacy was demonstrated in a phase II/III study on primary HLH pediatric patients with refractory, relapsing HLH or intolerance to first-line treatment. The use of emapalumab allowed most patients to proceed to HSCT, with a high estimated probability of survival 12 months after transplantation. The outcomes in patients who underwent transplantation compare favorably with those reported previously with either myeloablative or reduced-intensity conditioning regimens. The potential role of emapalumab in the treatment of secondary HLH and as a prevention of graft failure after HSCT deserves to be further assessed.