0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Investigation |

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

Tanya J. Williams, MD, PhD1; David R. Benavides, MD, PhD1; Kelly-Ann Patrice, MBBS1; Josep O. Dalmau, MD, PhD2,3; Alexandre Leon Ribeiro de Ávila, MD, PhD4; Dung T. Le, MD5; Evan J. Lipson, MD5; John C. Probasco, MD1; Ellen M. Mowry, MD, MCR1
[+] Author Affiliations
1Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland
2Department of Neurology, Hospital Clínic/Institut d'Investigació Biomèdica August Pi i Sunyer, University of Barcelona, Barcelona, Spain
3Institució Catalana de Recerca i Estudis Avançats, University of Barcelona, Barcelona, Spain
4Bristol-Myers Squibb, Plainsboro, New Jersey
5Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland
JAMA Neurol. 2016;73(8):928-933. doi:10.1001/jamaneurol.2016.1399.
Text Size: A A A
Published online

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.

Figures in this Article

Figures

Place holder to copy figure label and caption
Figure 1.
Timelines of Clinical Courses and Treatments for Patients With Autoimmune Encephalitis Associated With Nivolumab and Ipilimumab

A, Case 1. Anti–N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis in a patient with melanoma. B, Case 2. Autoimmune limbic encephalitis in a patient with small cell lung cancer (SCLC). CPM indicates cyclophosphamide; IL-2, interleukin 2; IV, intravenous; IVIG, intravenous immunoglobulin; MRI, magnetic resonance imaging; PD, progressive disease; PR, partial response per the Response Evaluation Criteria in Solid Tumors, guideline version 1.1.10BRAF gene (OMIM 164757).

aIndicates immunosuppressive therapy for paraneoplastic encephalitis.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.
Representative Brain Magnetic Resonance Images From a Patient With Autoimmune Limbic Encephalitis

A, Axial T2-weighted images demonstrate subtle hyperintensity of the right hippocampus (arrowhead) at the onset of neurologic symptoms in case 2. B, This abnormality resolved after treatment with oral corticosteroids, with corresponding symptomatic improvement.

Graphic Jump Location

Tables

References

Correspondence

CME


You need to register in order to view this quiz.

Multimedia

Some tools below are only available to our subscribers or users with an online account.

2,901 Views
0 Citations
×

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.

See Also...
Articles Related By Topic
Related Collections
PubMed Articles
Jobs
JAMAevidence.com

The Rational Clinical Examination: Evidence-Based Clinical Diagnosis

The Rational Clinical Examination: Evidence-Based Clinical Diagnosis

brightcove.createExperiences();