Emapalumab for adult and pediatric patients with hemophagocytic lymphohistiocytosis

Expert Rev Clin Pharmacol. 2021 May;14(5):527-534. doi: 10.1080/17512433.2021.1901576. Epub 2021 Mar 23.

Abstract

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.

Keywords: Emapalumab; chemotherapy; hemophagocytic lymphohistiocytosis; interferon-γ; monoclonal antibodies.

Publication types

  • Review

MeSH terms

  • Adult
  • Animals
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Neutralizing / administration & dosage*
  • Antibodies, Neutralizing / adverse effects
  • Antibodies, Neutralizing / pharmacology
  • Child
  • Disease Progression
  • Humans
  • Lymphohistiocytosis, Hemophagocytic / drug therapy*
  • Recurrence

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Emapalumab