Emapalumab in children with primary hemophagocytic lymphohistiocytosis: New England Journal of Medicine

F. Locatelli, M.B. Jordan, C. Allen, S. Cesaro, C. Rizzari, A. Rao, B. Degar, T.P. Garrington, J. Sevilla, M.-C. Putti, F. Fagioli, M. Ahlmann, J.-L. Dapena Diaz, M. Henry, F. de Benedetti, A. Grom, G. Lapeyre, P. Jacqmin, M. Ballabio, C. de Min

Research output: Contribution to journalArticlepeer-review

Abstract

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. © 2020 Massachusetts Medical Society.
Original languageEnglish
Pages (from-to)1811-1822
Number of pages12
JournalNew Engl. J. Med.
Volume382
Issue number19
DOIs
Publication statusPublished - 2020

Keywords

  • dexamethasone
  • emapalumab
  • antiinflammatory agent
  • CXCL9 chemokine
  • CXCL9 protein, human
  • gamma interferon
  • monoclonal antibody
  • neutralizing antibody
  • adolescent
  • Article
  • child
  • clinical article
  • drug efficacy
  • drug safety
  • drug withdrawal
  • female
  • hemophagocytic syndrome
  • histoplasmosis
  • human
  • infant
  • infection
  • male
  • multicenter study
  • phase 2 clinical trial
  • phase 3 clinical trial
  • primary hemophagocytic lymphohistiocytosis
  • priority journal
  • prospective study
  • blood
  • clinical trial
  • combination drug therapy
  • complication
  • etiology
  • hematopoietic stem cell transplantation
  • Kaplan Meier method
  • mortality
  • onset age
  • preschool child
  • treatment outcome
  • Adolescent
  • Age of Onset
  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Chemokine CXCL9
  • Child
  • Child, Preschool
  • Dexamethasone
  • Drug Therapy, Combination
  • Female
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Infant
  • Infections
  • Interferon-gamma
  • Kaplan-Meier Estimate
  • Lymphohistiocytosis, Hemophagocytic
  • Male
  • Treatment Outcome

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