Abstract
Objective To report the induction of anti–Ma2 antibody–associated paraneoplastic neurologic syndrome (Ma2-PNS) in 6 patients after treatment with immune checkpoint inhibitors (ICIs). We also analyzed (1) patient clinical features compared with a cohort of 44 patients who developed Ma2-PNS without receiving ICI treatment and (2) the frequency of neuronal antibody detection before and after ICI implementation.
Methods Retrospective nationwide study of all patients with Ma2-PNS developed during ICI treatment between 2017 and 2018.
Results Our series of patients included 5 men and 1 woman (median age, 63 years). The patients were receiving nivolumab (n = 3), pembrolizumab (n = 2), or a combination of nivolumab and ipilimumab (n = 1) for treatment of neoplasms that included lung (n = 4) and kidney (n = 1) cancers and pleural mesothelioma (n = 1). Clinical syndromes comprised a combination of limbic encephalitis and diencephalitis (n = 3), isolated limbic encephalitis (n = 2), and a syndrome characterized by ophthalmoplegia and head drop (n = 1). No significant clinical difference was observed between our 6 patients and the overall cohort of Ma2-PNS cases. Post-ICI Ma2-PNS accounted for 35% of the total 17 Ma2-PNS diagnosed in our center over the 2017–2018 biennium. Eight cases had been detected in the preceding biennium 2015–2016, corresponding to a 112% increase of Ma2-PNS frequency since the implementation of ICIs in France. Despite ICI withdrawal and immunotherapy, 4/6 patients died, and the remaining 2 showed a moderate to severe disability.
Conclusions We show a clear association between ICI use and increased diagnosis of Ma2-PNS. Physicians need to be aware that ICIs can trigger Ma2-PNS because clinical presentation can be challenging.
Glossary
- CBA=
- cell-based assay;
- CTLA-4=
- cytotoxic T lymphocyte–associated antigen 4;
- ICI=
- immune checkpoint inhibitor;
- irAE=
- immune-related adverse event;
- Ma2-PNS=
- Ma2 antibody–associated paraneoplastic neurologic syndrome;
- mRS=
- modified Ranking Scale;
- NMDAR=
- NMDA receptor;
- PD-1=
- programmed death-1 receptor
Footnotes
Go to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article.
↵* These authors contributed equally to the manuscript.
Data access, responsibility, and analysis: The corresponding author had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
The Article Processing Charge was funded by Institut Neuromyogène INSERM U1217 CNRS 5310.
- Received April 24, 2019.
- Accepted in final form July 8, 2019.
- Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
Letters: Rapid online correspondence
- Author response: Increased frequency of anti-Ma2 encephalitis associated with immune checkpoint inhibitors
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