Treatment of Refractory Anti-NMDA Receptor Encephalitis with Daratumumab in Two Pediatric Patients
Amy Young1, Abby Kunz3, Jordan Abbott2, Amanda Piquet1, Teri Schreiner4, Ryan Kammeyer5
1University of Colorado, 2Pediatric Allergy Immunology, University of Colorado, 3Presbyterian Medical Group, 4University of Colorado/ Children's Hospital of Colorado, 5Childrens Hospital Colorado
Objective:
To highlight two cases of treatment-refractory pediatric anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis with favorable responses to daratumumab.
Background:
Anti-NMDAR encephalitis presents with neuropsychiatric symptoms, autonomic instability and seizures frequently leading to ICU admissions. Corticosteroids are recommended in all children with anti-NMDAR encephalitis with IVIg or plasma exchange as additional first-line therapies.  Second-line therapies (rituximab and cyclophosphamide) should be considered 2 weeks after first-line therapies with further escalation to an additional second-line medication or tocilizumab in refractory cases after 1-3 months. Daratumumab is a humanized monoclonal anti-CD38 antibody which targets plasma cells. There are reports using daratumumab in adult autoimmune encephalitis (AIE), with very few described cases in pediatric AIE.
Design/Methods:

Retrospective case series.

Results:

A 9-year-old boy presented with seizures, right arm numbness and weakness and hallucinations. Workup was notable for MRI brain with biparietal cortical/subcortical edema and positive cerebrospinal fluid (CSF) anti-NMDAR antibodies. He was initially treated with IVIg, steroids and rituximab. Over the course of 3 years, he had waxing and waning aggression, anxiety and psychosis despite initial response to additional immunotherapies, including cyclophosphamide, plasma exchange, tocilizumab, mycophenolate. Finally after the addition of daratumumab he had near complete resolution of his neuropsychiatric symptoms. He is now stable on monthly maintenance daratumumab and replacement IVIg.

A 16-year-old adolescent girl presented with behavior change, hallucinations and seizures prompting workup for AIE, which revealed CSF anti-NMDA receptor antibodies. She started IVIg, steroids plasma exchange and rituximab. However, 5 months after initial presentation she had persistent aggression, hallucinations, and seizures. PLEX was repeated and Daratumumab was administered with significant improvement in her behavioral and psychiatric symptoms, followed by return to school.

Conclusions:

In this report, we describe two cases of pediatric anti-NMDAR encephalitis that responded to daratumumab, highlighting a potential therapeutic option to be explored in treatment-refractory cases.

10.1212/WNL.0000000000205325