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Cited by 276

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Association of Autoimmune Encephalitis With Combined Immune Checkpoint Inhibitor Treatment for Metastatic Cancer

Williams, Tanya J., Benavides, David R., Patrice, Kelly-Ann, Dalmau, Josep O., de Ávila, Alexandre Leon Ribeiro, Le, Dung T., Lipson, Evan J., Probasco, John C., Mowry, Ellen M.·2016·JAMA Neurology

Abstract

IMPORTANCE: Paraneoplastic encephalitides usually precede a diagnosis of cancer and are often refractory to immunosuppressive therapy. Conversely, autoimmune encephalitides are reversible conditions that can occur in the presence or absence of cancer. OBJECTIVE: To report the induction of autoimmune encephalitis in 2 patients after treatment of metastatic cancer with a combination of the immune checkpoint inhibitors nivolumab and ipilimumab. DESIGN, SETTING, AND PARTICIPANTS: A retrospective case study was conducted of the clinical and management course of 2 patients with progressive, treatment-refractory metastatic cancer who were treated with a single dose each (concomitantly) of the immune checkpoint inhibitors nivolumab, 1 mg/kg, and ipilimumab, 3 mg/kg. EXPOSURES: Nivolumab and ipilimumab. MAIN OUTCOMES AND MEASURES: The clinical response to immunosuppressive therapy in suspected autoimmune encephalitis in the setting of immune checkpoint inhibitor use. RESULTS: Autoantibody testing confirmed identification of anti-N-methyl-D-aspartate receptor antibodies in the cerebrospinal fluid of 1 patient. Withdrawal of immune checkpoint inhibitors and initiation of immunosuppressive therapy, consisting of intravenous methylprednisolone sodium succinate equivalent to 1000 mg of methylprednisolone for 5 days, 0.4 mg/kg/d of intravenous immunoglobulin for 5 days, and 2 doses of rituximab, 1000 mg, in 1 patient and oral prednisone, 60 mg/d, in the other patient, resulted in improved neurologic symptoms. CONCLUSIONS AND RELEVANCE: Immune checkpoint inhibition may favor the development of immune responses against neuronal antigens, leading to autoimmune encephalitis. Early recognition and treatment of autoimmune encephalitis in patients receiving immune checkpoint blockade therapy will likely be essential for maximizing clinical recovery and minimizing the effect of drug-related toxic effects. The mechanisms by which immune checkpoint inhibition may contribute to autoimmune encephalitis require further study.

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Crossref · 10.1001/jamaneurol.2016.1399

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Metadata

Authors
Williams, T. J., Benavides, D. R., Patrice, K.-A., Dalmau, J. O., de Ávila, A. L. R., Le, D. T., Lipson, E. J., Probasco, J. C., & Mowry, E. M.
Venue
JAMA Neurology
Published
2016-08-01
Volume
73
Issue
8
Pages
928
ISSN
2168-6149 (ISSN-L)
OpenAlex
W2411407183
Cited by
276
References
4
FWCI
24.67
Type
journal article
Language
en
Open access
closed

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