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Daratumumab treatment for therapy-refractory anti-CASPR2 encephalitis

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The anti-CD38 antibody daratumumab is approved for treatment of refractory multiple myeloma and acts by depletion of plasma cells and modification of various T-cell functions. Its safety, immunological effects and therapeutic potential was evaluated in a 60-year old patient with life-threatening and treatment-refractory anti-CASPR2 encephalitis requiring medical care and artificial ventilation in an intensive care unit. His autoimmune dysfunction was driven by exceptional high anti-CASPR2 autoantibody titers combined with an abnormally increased T-cell activation. As he remained unresponsive to standard and escalation immunotherapies (methylprednisolone, plasma exchange, immunoadsorption, immunoglobulins, rituximab and bortezomib), therapy was escalated to 13 cycles of 16 mg/kg daratumumab. During the treatment period, clinical, radiological, histological and laboratory findings, including quantification of autoreactive and protective antibody levels and FACS-based immune phenotyping, were analyzed. Daratumumab treatment was associated with significant clinical improvement, substantial reduction of anti-CASPR2 antibody titers, especially in CSF, decrease of immunoglobulin levels and protective vaccine titers, as well as normalization of initially increased T-cell activation markers. However, the patient died of Gram-negative septicemia in a neurorehabilitation center. In conclusion, our findings suggest that daratumumab induces not only depletion of autoreactive long-lived plasma cells associated with improvements of neurological sequelae, but also severe side effects requiring clinical studies investigating efficacy and safety of anti-CD38 therapy in antibody-driven autoimmune encephalitis.

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Central nervous system


Intensive care unit


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The study was funded by NeuroCure Excellence Cluster (EXC 257). We thank our patient and his next of kin for participation in this study.

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Correspondence to Franziska Scheibe.

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The authors declare that they have no conflict of interest.

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This is a retrospective clinical case report and not a clinical study, approval by an ethic committee was not necessary.

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Written informed consent for treatment and publication was given by patient’s next of kin.

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Scheibe, F., Ostendorf, L., Reincke, S.M. et al. Daratumumab treatment for therapy-refractory anti-CASPR2 encephalitis. J Neurol 267, 317–323 (2020).

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