Ofatumumab treatment for nephrotic syndrome recurrence after pediatric renal transplantation.


Journal

Pediatric nephrology (Berlin, Germany)
ISSN: 1432-198X
Titre abrégé: Pediatr Nephrol
Pays: Germany
ID NLM: 8708728

Informations de publication

Date de publication:
08 2020
Historique:
received: 28 08 2019
accepted: 02 04 2020
revised: 30 03 2020
pubmed: 20 4 2020
medline: 23 6 2021
entrez: 20 4 2020
Statut: ppublish

Résumé

Relapsing nephrotic syndrome (NS) after transplantation can be a challenge to treat. The result of the consequent long-lasting proteinuria is the loss of the graft. Disease recurrence after renal transplantation occurs in around half of cases, and the efficacy of therapeutic strategies is often limited. Recently, ofatumumab, a second-generation and fully human anti-CD20 monoclonal antibody, has been shown to be effective in severe situations. We retrospectively collected data from the medical records of children with recurrence of NS after renal transplantation treated with ofatumumab in France, after failure of previous treatments. Six patients were included in this study in five centers with a median duration of follow-up of 10.5 months. Two different ofatumumab regimens were administered. The primary outcome was proteinuria at 6 months after the last dose of ofatumumab. No patient achieved a complete remission, 3/6 had a partial remission, and 3/6 had no response to ofatumumab. Four patients exhibited a minor allergic reaction with the first infusion. One patient died of infection, as a consequence of multiple factors. No malignancies were observed; however, the time of follow-up was not sufficient to see such disease. Altogether, these results suggest ofatumumab has a poor efficacy in treating recurrence of NS after renal transplantation. However, it could be discussed in multidrug-resistant refractory NS, but infectious complications and overimmunosuppression have to be balanced. There is a need for further studies to confirm these findings and safety and to determine a standardized protocol in this indication.

Sections du résumé

BACKGROUND
Relapsing nephrotic syndrome (NS) after transplantation can be a challenge to treat. The result of the consequent long-lasting proteinuria is the loss of the graft. Disease recurrence after renal transplantation occurs in around half of cases, and the efficacy of therapeutic strategies is often limited. Recently, ofatumumab, a second-generation and fully human anti-CD20 monoclonal antibody, has been shown to be effective in severe situations.
METHODS
We retrospectively collected data from the medical records of children with recurrence of NS after renal transplantation treated with ofatumumab in France, after failure of previous treatments.
RESULTS
Six patients were included in this study in five centers with a median duration of follow-up of 10.5 months. Two different ofatumumab regimens were administered. The primary outcome was proteinuria at 6 months after the last dose of ofatumumab. No patient achieved a complete remission, 3/6 had a partial remission, and 3/6 had no response to ofatumumab. Four patients exhibited a minor allergic reaction with the first infusion. One patient died of infection, as a consequence of multiple factors. No malignancies were observed; however, the time of follow-up was not sufficient to see such disease.
CONCLUSIONS
Altogether, these results suggest ofatumumab has a poor efficacy in treating recurrence of NS after renal transplantation. However, it could be discussed in multidrug-resistant refractory NS, but infectious complications and overimmunosuppression have to be balanced. There is a need for further studies to confirm these findings and safety and to determine a standardized protocol in this indication.

Identifiants

pubmed: 32306087
doi: 10.1007/s00467-020-04567-7
pii: 10.1007/s00467-020-04567-7
doi:

Substances chimiques

Antibodies, Monoclonal, Humanized 0
Immunosuppressive Agents 0
ofatumumab M95KG522R0

Types de publication

Journal Article Multicenter Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

1499-1506

Auteurs

Josselin Bernard (J)

Pediatric Department, University Hospital of Nantes, Nantes, France. joss.bernard@gmail.com.
Service de Maladies Chroniques de l'enfant, Hôpital femme-enfants-adolescent, CHU Nantes, 7, quai Moncousu, 44093, Cedex Nantes, France. joss.bernard@gmail.com.

Fanny Lalieve (F)

Pediatric Department, University Hospital of Bordeaux, Bordeaux, France.

Julie Sarlat (J)

Pediatric Department, University Hospital of Toulouse, Toulouse, France.

Justine Perrin (J)

Pediatric Department, University Hospital of Marseille, Marseille, France.

Laurene Dehoux (L)

Pediatric Nephrology Department, University Hospital of Necker Enfants Malades, APHP, Paris, France.

Olivia Boyer (O)

Pediatric Nephrology Department, University Hospital of Necker Enfants Malades, APHP, Paris, France.

Astrid Godron-Dubrasquet (A)

Pediatric Department, University Hospital of Bordeaux, Bordeaux, France.

Jerome Harambat (J)

Pediatric Department, University Hospital of Bordeaux, Bordeaux, France.

Stephane Decramer (S)

Pediatric Department, University Hospital of Toulouse, Toulouse, France.

Mathilde Caillez (M)

Pediatric Department, University Hospital of Marseille, Marseille, France.

Alexandra Bruel (A)

Pediatric Department, University Hospital of Nantes, Nantes, France.
Service de Maladies Chroniques de l'enfant, Hôpital femme-enfants-adolescent, CHU Nantes, 7, quai Moncousu, 44093, Cedex Nantes, France.

Emma Allain-Launay (E)

Pediatric Department, University Hospital of Nantes, Nantes, France.
Service de Maladies Chroniques de l'enfant, Hôpital femme-enfants-adolescent, CHU Nantes, 7, quai Moncousu, 44093, Cedex Nantes, France.

Jacques Dantal (J)

Nephrology and Immunology Department, University Hospital of Nantes, Nantes, France.

Gwenaëlle Roussey (G)

Pediatric Department, University Hospital of Nantes, Nantes, France.
Service de Maladies Chroniques de l'enfant, Hôpital femme-enfants-adolescent, CHU Nantes, 7, quai Moncousu, 44093, Cedex Nantes, France.

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Classifications MeSH