Emapalumab may be an effective therapy for pediatric patients with primary hemophagocytic lymphohistiocytosis (HLH), according to research published in The New England Journal of Medicine.

Primary HLH, a rare disorder associated with immune activation and inflammation, often manifests during infancy and is nearly always fatal if left untreated and is fatal with treatment in 40% of cases. While primary HLH is heterogeneous, it is characterized by attenuated cytotoxic function of natural killer and CD8+ T cells.

The primary objective of primary HLH treatment has been to suppress immune activation and inflammation to permit allogeneic hematopoietic stem cell transplantation (AHSCT), the only therapy associated with a cure. However, adverse events caused by treatment, especially general immunosuppression are linked to mortality, further highlighting the need for novel therapies in this setting.

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Emapalumab is a monoclonal antibody targeting interferon-gamma, and in an open-label phase 2/3 study (ClinicalTrials.gov Identifier: NCT01818492 and NCT02069899), researchers enrolled 34 patients with primary HLH to determine the drug’s safety and efficacy. A total of 27 patients had previously undergone treatment for primary HLH, while 7 had untreated disease; 26 patients completed the study.

The overall median age at diagnosis was 0.85 years, 53% of patients were female, and the most common genomic variants observed were FLH3 (24% of patients) and FLH2 (21% of patients). The median duration of treatment was 48 days among those who had received previous treatment compared with 59 days among all patients.

Sixty-five percent of patients who received emapalumab infusion and 63% of previously treated patients had a response. Among previously treated patients, 26% had a complete response and 30% had a partial response; complete and partial response rates for patients who received emapalumab were 21% and 32%, respectively. C-X-C motif chemokine ligand 9 levels at the end of treatment were associated with a lower likelihood of response.

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At the end of the study, 71% of patients were alive and, of the 10 patients who passed away, no deaths were considered by the authors to be linked to study treatment. All patients experienced at least 1 adverse event and of the 13 infections reported as serious adverse events, 1 led to fatal septic shock after the second experimental infusion.

“In conclusion, in this study, emapalumab was effective with a low level of toxic effects in patients with primary hemophagocytic lymphohistiocytosis,” the authors wrote.


Locatelli F, Jordan MB, Allen C, et al. Emapalumab in children with primary hemophagocytic lymphohistiocytosis. N Engl J Med. 2020;382(19):1811‐1822.