Short CommunicationWorsening of anti-Hu paraneoplastic neurological syndrome related to anti-PD-1 treatment: Case report and review of literature
Graphical abstract
Section snippets
Background
Immune checkpoint inhibitors (ICI) have revolutionized the treatment of cancer resulting in increased survival. While ICI enhance anti-tumor immune reactivity resulting in tumor regression they also reduce immune tolerance towards self-antigen and predispose to the development of autoimmunity (Postow et al., 2018). This leads to a wide spectrum of immune-mediated central and peripheral nervous system disorders. Although serious neurologic immune-related adverse events (nirAE) are seen in less
Case presentation
A 62-year-old woman presented with numbness in her hands and feet, tremor, loss of dexterity, and gait ataxia over a two-month period. She also noted excessive fatigue, altered taste, and 30 pounds weight loss. Her examination showed pseudoathetoid movements of both hands; there was reduced sensation to all modalities in a stocking-glove distribution, in the distal third of upper and lower extremities. She had dysmetria on finger-nose testing on left and intention tremor on right.
Review of literature
A Medline and Google Scholar search for “nivolumab” or “immune-checkpoint inhibitor” or “pembrolizumab” or “cemiplimab” combined with “anti-Hu antibody” or “paraneoplastic syndrome” or “encephalitis” revealed 6 cases of anti-Hu PNS with anti-PD-1 inhibitor use; they are all listed in Table 1.
Discussion
This case highlights several key points. Nivolumab caused worsening of pre-existing anti-Hu paraneoplastic sensory neuronopathy associated with small cell lung cancer. The worsening of PNS with nivolumab was associated with elevated titers of onconeural antibodies with no signs of cancer recurrence; this is suggestive of nirAE. Furthermore, there was no improvement in symptoms despite stopping nivolumab and treatment with high dose corticosteroids and IV Ig. Finally, elevated titers of anti-Hu
Conclusion
ICI are novel treatments with a promise of cancer remission, but they can induce a wide spectrum of immune-mediated neurologic adverse events. PNS are associated with poor prognosis with significant morbidity, and if these patients are treated with anti-PD-1 inhibitors there may be worsening of their PNS. Timely identification of PNS in cancer patients, and monitoring for worsening of pre-existing PNS when treating these patients with ICI, may help prevent long term disability and death. The
Declaration of Competing interest
PR- The author declares that she has no competing interests.
DH- The author declares that she has no competing interests.
KG- The author serves on advisory boards for Sanofi Genzyme and Eli Lilly.
JS- The author declares that she has no competing interests.
Acknowledgements
None.
This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.
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