Immune mediated neuropathy following checkpoint immunotherapy

J Clin Neurosci. 2017 Nov:45:14-17. doi: 10.1016/j.jocn.2017.07.014. Epub 2017 Jul 29.

Abstract

Checkpoint immunotherapy has revolutionised cancer therapy and is now standard treatment for many malignancies including metastatic melanoma. Acute inflammatory neuropathies, often labelled as Guillain-Barre syndrome, are an uncommon but potentially severe complication of checkpoint immunotherapy with individual cases described but never characterised as a group. We describe a case of acute sensorimotor and autonomic neuropathy following a single dose of combination ipilimumab and nivolumab for metastatic melanoma. A literature search was performed, identifying 14 other cases of acute neuropathy following checkpoint immunotherapy, with the clinical, electrophysiological and laboratory features summarised. Most cases described an acute sensorimotor neuropathy (92%) with hyporeflexia (92%) that could occur from induction up till many weeks after the final dose of therapy. In contrast to Guillain-Barre syndrome, the cerebrospinal fluid (CSF) analysis often shows a lymphocytic picture (50%) and the electrophysiology showed an axonal pattern (55%). Treatment was variable and often in combination. 11 cases received steroid therapy with only 1 death within this group, whereas of the 4 patients who did not receive steroid therapy there were 3 deaths. In conclusion checkpoint immunotherapy - induced acute neuropathies are distinct from and progress differently to Guillain-Barre syndrome. As with other immunotherapy related adverse events corticosteroid therapy should be initiated in addition to usual therapy.

Keywords: CTLA-4, PD-1; Checkpoint immunotherapy; Guillain-Barre; Ipilimumab; Neuropathy; Nivolumab.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adult
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols
  • Female
  • Humans
  • Immunotherapy / adverse effects*
  • Ipilimumab / administration & dosage
  • Ipilimumab / adverse effects*
  • Ipilimumab / therapeutic use
  • Melanoma / pathology
  • Melanoma / therapy*
  • Neoplasm Metastasis
  • Nivolumab
  • Peripheral Nervous System Diseases / etiology*
  • Peripheral Nervous System Diseases / pathology

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Ipilimumab
  • Nivolumab