Daratumumab Treatment in Severe Anti-NMDAR Encephalitis: Two Case Reports and Literature Review.

Authors

Nady Ammar, Marjolaine Uginet, Pia De Stefano, Hervé Quintard, Kaveh Samii, Jörg D Seebach, Josep Dalmau, Patrice H Lalive

Published in

Neurology(R) neuroimmunology & neuroinflammation. Volume 13. Issue 6. Pages e200648. Epub Sep 09, 2026.

Abstract

To describe clinical outcomes following daratumumab therapy in severe anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis, including a literature review.
We report 2 patients with severe anti-NMDAR encephalitis treated with anti-CD38 daratumumab after failure of multiple immunotherapies. Clinical data, treatments, and outcomes were analyzed retrospectively. A PubMed literature review identified 4 additional cases.
Both patients (21 and 19 years) presented with severe anti-NMDAR encephalitis characterized by neuropsychiatric symptoms, seizures, abnormal movements, and dysautonomia. Modified Rankin Scale (mRS) reached rapidly 5 in both cases and required ICU transfer within the first 2 weeks of hospitalization. Despite high-dose methylprednisolone, IV immunoglobulin, plasma exchange, rituximab, and cyclophosphamide, neither patient showed improvement. Daratumumab (1800 mg s/c) was initiated 40 and 14 weeks after onset, respectively. Clinical improvement occurred within weeks after treatment initiation, with gradual recovery of cognitive and functional abilities and ultimately regained functional independence (mRS 0). Literature review identified 4 additional cases of anti-NMDAR encephalitis treated with daratumumab; most patients showed substantial neurologic improvement.
These observations suggest that specific plasma cell-targeted therapy may be beneficial in severe anti-NMDAR encephalitis, potentially through reduction of pathogenic autoantibody production. However, current evidence is limited to uncontrolled reports, and further studies are needed to clarify optimal timing, efficacy, and safety.

PMID:
42715496
Bibliographic data and abstract were imported from PubMed on 10 Sep 2026.

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