Emapalumab in Children with Primary Hemophagocytic Lymphohistiocytosis
Open accessAbstract
BACKGROUND: Primary hemophagocytic lymphohistiocytosis is a rare syndrome characterized by immune dysregulation and hyperinflammation. It typically manifests in infancy and is associated with high mortality. METHODS: We investigated the efficacy and safety of emapalumab (a human anti-interferon-γ antibody), administered with dexamethasone, in an open-label, single-group, phase 2-3 study involving patients who had received conventional therapy before enrollment (previously treated patients) and previously untreated patients who were 18 years of age or younger and had primary hemophagocytic lymphohistiocytosis. The patients could enter a long-term follow-up study until 1 year after allogeneic hematopoietic stem-cell transplantation or until 1 year after the last dose of emapalumab, if transplantation was not performed. The planned 8-week treatment period could be shortened or extended if needed according to the timing of transplantation. The primary efficacy end point was the overall response, which was assessed in the previously treated patients according to objective clinical and laboratory criteria. RESULTS: At the cutoff date of July 20, 2017, a total of 34 patients (27 previously treated patients and 7 previously untreated patients) had received emapalumab; 26 patients completed the study. A total of 63% of the previously treated patients and 65% of the patients who received an emapalumab infusion had a response; these percentages were significantly higher than the prespecified null hypothesis of 40% (P = 0.02 and P = 0.005, respectively). In the previously treated group, 70% of the patients were able to proceed to transplantation, as were 65% of the patients who received emapalumab. At the last observation, 74% of the previously treated patients and 71% of the patients who received emapalumab were alive. Emapalumab was not associated with any organ toxicity. Severe infections developed in 10 patients during emapalumab treatment. Emapalumab was discontinued in 1 patient because of disseminated histoplasmosis. CONCLUSIONS: Emapalumab was an efficacious targeted therapy for patients with primary hemophagocytic lymphohistiocytosis. (Funded by NovImmune and the European Commission; NI-0501-04 and NI-0501-05 ClinicalTrials.gov numbers, NCT01818492 and NCT02069899.).
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Emapalumab, a monoclonal antibody that binds interferon-γ, was recently approved for the treatment of cytokine storm in patients with primary HLH.
“Emapalumab, a monoclonal antibody that binds interferon-γ, was recently approved for the treatment of cytokine storm in patients with primary HLH.”
From Cytokine storm (2020) · cites this paper as [32]
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- Authors
- Locatelli, F., Jordan, M. B., Allen, C., Cesaro, S., Rizzari, C., Rao, A., Degar, B., Garrington, T. P., Sevilla, J., Putti, M.-C., Fagioli, F., Ahlmann, M., Dapena Diaz, J.-L., Henry, M., De Benedetti, F., Grom, A., Lapeyre, G., Jacqmin, P., Ballabio, M., & de Min, C.
- Affiliations
- Azienda Ospedaliera Universitaria Integrata Verona (IT)
- Baylor College of Medicine (US)
- Great Ormond Street Hospital (GB)
- From the Department of Pediatrics, Sapienza, University of Rome (F.L.), and the Department of Pediatric Hematology–Oncology (F.L.) and Division of Rheumatology (F.D.B.), IRCCS Bambino Gesù Children’s Hospital, Rome, Pediatric Hematology–Oncology, Woman and Child Hospital, Azienda Ospedaliera Universitaria Integrata, Verona (S.C.), the Pediatric Hematology–Oncology Unit, Department of Pediatrics, University of Milano–Bicocca, Monza Brianza per il Bambino e la sua Mamma Foundation, Monza (C.R.), the...
- University of Padua (IT)
- University of Münster (DE)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2020-05-07
- Volume
- 382
- Issue
- 19
- Pages
- 1811-1822
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W3021363743
- Cited by
- 534
- References
- 26
- Citations by year
- 2026: 72 · 2025: 70 · 2024: 88 · 2023: 70 · 2022: 89 · 2021: 96 · 2020: 47
- FWCI
- 47.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, other-oa)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
- BOA (University of Milano-Bicocca) (submittedVersion)
- Funders
- European Commission
- Topics
- Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Health Sciences › Medicine › Surgery › Kawasaki Disease and Coronary Complications
- Keywords
- primary hemophagocytic lymphohistiocytosis, emapalumab, anti-interferon-gamma antibody, hyperinflammation, immune dysregulation, dexamethasone, allogeneic hematopoietic stem cell transplantation, previously treated patients, serious infections, histoplasmosis, targeted therapy, pediatric patients, overall response, drug safety
- MeSH terms
- Adolescent, Anti-Inflammatory Agents, Antibodies, Monoclonal, Child, Child, Preschool, Dexamethasone, Drug Therapy, Combination, Female, Humans, Infant, Infections, Interferon-gamma, Male, Treatment Outcome, Age of Onset, Hematopoietic Stem Cell Transplantation, Lymphohistiocytosis, Hemophagocytic, Kaplan-Meier Estimate, Chemokine CXCL9, Antibodies, Neutralizing
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