Neutralizing interferon-γ with emapalumab appears to be safe and efficacious in children with primary hemophagocytic lymphohistiocytosis (HLH), according to a recent study published in The New England Journal of Medicine.

The investigators conducted the open-label, single-group, phase 2-3 study ( Identifier: NCT01818492) on safety and efficacy of the human anti–interferon-γ antibody, emapalumab, administered with dexamethasone, in patients with HLH who were previously treated with conventional therapy or were treatment naive.

“The objective of treatment for primary hemophagocytic lymphohistiocytosis is to suppress inflammation in order to allow for allogeneic hematopoietic stem-cell transplantation, the only curative therapy for this disease,” wrote the authors.

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After the last dose of emapalumab or, if received, after allogeneic hematopoietic stem-cell transplantation (allo-HSCT), the patients could enter a long-term follow-up study ( Identifier: NCT02069899). The treatment period was shortened or lengthened according to the patients’ needs for transplantation. The primary endpoint was overall response. Follow-up data was collected until 12 months after transplantation, and the regulatory cutoff date was July 20, 2017.

At data cutoff, 27 previously treated (median age, 1.00 year; range, 0.2-13.0) and 34 treatment-naive patients (median age, 1.00 year; range, 0.1-13.0) were administered emapalumab. After 8 weeks of emapalumab treatment, 63% and 65% of the previously treated patients and the treatment-naive patients, respectively, had a response; both treatment groups achieved significantly higher response rates than the study’s prespecified null hypothesis of 40% (P =.02 and P =.005, respectively).

Most patients in both treatment groups were able to proceed to transplantation: 70% (19/27) of previously treated patients and 65% (22/34) of treatment-naive patients. At 12 months after transplantation, the estimated probability of survival was 89.5% (95% CI, 64.1-97.3) for previously treated patients and 90.2% (95% CI, 66.2-97.5) for treatment-naive patients. At 20 months, 74% of the previously treated patients and 71% of the treatment-naive patients were alive. No deaths were considered to be related to emapalumab.

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According to the investigators, emapalumab was not associated with organ toxicity and did not appear to exacerbate the adverse events associated with the disease. At the start of the study, 35% of patients had ongoing infection or positive microbiologic tests, and during treatment, 10 patients developed severe infections. Treatment was discontinued in 1 patient (disseminated histoplasmosis).

“In conclusion, in this study, emapalumab was effective with a low level of toxic effects in patients with primary hemophagocytic lymphohistiocytosis. The study provides support for further investigation of emapalumab in patients with secondary forms of hemophagocytic lymphohistiocytosis in whom interferon-γ has been suggested to be pathogenic,” concluded the authors.

Disclosures: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


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