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-γ) plays a key pathogenic role. 
Emapalumab, a monoclonal antibody directed against IFN-γ, 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.