Association of autoimmune encephalitis with combined immune checkpoint inhibitor treatment for metastatic cancer

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 studywas conducted of the clinical and management course of 2 patients with progressive, treatment-refractorymetastatic cancer who were treated with a single dose each (concomitantly) of the immune checkpoint inhibitors nivolumab, 1mg/kg, and ipilimumab, 3mg/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 1000mg of methylprednisolone for 5 days, 0.4mg/kg/d of intravenous immunoglobulin for 5 days, and 2 doses of rituximab, 1000mg, in 1 patient and oral prednisone, 60mg/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.