Short Communication
Worsening of anti-Hu paraneoplastic neurological syndrome related to anti-PD-1 treatment: Case report and review of literature

https://doi.org/10.1016/j.jneuroim.2020.577184Get rights and content

Highlights

  • Immune checkpoint inhibitors (ICI) have the potential to worsen pre-existing anti-Hu paraneoplastic neurologic syndrome (PNS).

  • Two of the three patients with known anti-Hu antibody prior to introduction of anti-PD-1 inhibitor died and the other one had severe disability.

  • The decision to start ICI in patients with pre-existing PNS should be carefully evaluated after having a risks and benefits discussion.

Abstract

We present an illustrative case of a 62-year-old woman with small cell lung cancer who developed progressive worsening of pre-existing anti-Hu antibody associated sensory neuronopathy after treatment with programmed cell death-1 (PD-1) inhibitor, nivolumab. We review the literature and identify 6 reported cases to understand the clinical outcomes of patients with anti-Hu paraneoplastic neurologic syndrome (PNS) treated with anti-PD-1 treatment.

The PNS clinical spectrum comprised of encephalitis, a combination of sensory neuronopathy and anti-NMDAR encephalitis, isolated sensory neuronopathy, and encephalomyelitis. Immune checkpoint inhibitor have the potential to worsen pre-existing anti-Hu PNS and may promote the development of anti-Hu PNS.

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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