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


METHODS
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.


METHODS
Nivolumab and ipilimumab.


METHODS
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
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.
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Tanya J
TJ
Williams
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
David R
DR
Benavides
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Kelly-Ann
KA
Patrice
Department of Neurology, Hospital Clínic/Institut d'Investigació Biomèdica August Pi i Sunyer, University of Barcelona, Barcelona, Spain3Institució Catalana de Recerca i Estudis Avançats, University of Barcelona, Barcelona, Spain.
Josep O
JO
Dalmau
Bristol-Myers Squibb, Plainsboro, New Jersey.
Alexandre Leon Ribeiro
AL
de Ávila
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Dung T
DT
Le
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Evan J
EJ
Lipson
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
John C
JC
Probasco
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Ellen M
EM
Mowry
D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D004359:Drug Therapy, Combination / Q000009:adverse effects; D004660:Encephalitis / Q000139:chemically induced*; D005260:Female; D050031:Hashimoto Disease / Q000139:chemically induced*; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects*; D000074324:Ipilimumab; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000556:secondary; D008875:Middle Aged; D000077594:Nivolumab; D012189:Retrospective Studies; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy / Q000556:secondary
D000911:Antibodies, Monoclonal; D007155:Immunologic Factors; D000074324:Ipilimumab; D000077594:Nivolumab