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Comparison of immune checkpoint inhibitor-related neuropathies among patients with neuroendocrine and non-neuroendocrine tumours
  1. Pitcha Chompoopong1,
  2. Anastasia Zekeridou1,2,
  3. Shahar Shelly1,
  4. Michel Ruff1,
  5. P James Dyck1,
  6. C J Klein1,
  7. Sean J Pittock1,2,
  8. Michelle Mauermann1,
  9. Divyanshu Dubey1,2
  1. 1 Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA
  2. 2 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
  1. Correspondence to Dr Divyanshu Dubey, Department of Neurology, Mayo Clinic, Rochester 55905, Minnesota, USA; Dubey.Divyanshu{at}

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Immune checkpoint inhibitor (ICI) indications have broadened considerably in the last few years.1 The aim of this study is to provide an update on clinical presentations, serological associations and outcomes of ICI-related neuropathy (irNeuropathy) in the context of expanding use of cancer immunotherapy for neuroendocrine tumours.


All patients with irNeuropathy who were evaluated at Mayo Clinic from 01 January 2015 to 10 October 2020 were identified by electronic medical record search. Patients with neuropathies secondary to cytotoxic chemotherapy, radiation, diabetes, structural or compressive aetiologies, prior to administration of ICIs were excluded. Clinical presentations, electrodiagnostic features, autoantibody profiles and clinical outcomes were reviewed.


Twenty patients (13 males) with irNeuropathy were identified. Median age was 64 (range 31–81) years. Two patients (10%) had a diagnosis of autoimmune disorders prior to ICI initiation; one with Graves’ disease and the other with rheumatoid arthritis. ICI regimens included programmed cell death-1 receptor (PD-1) or programmed death-ligand 1 inhibitors (n=15, 75%), cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitor (n=2, 10%) and a combination of PD-1 and CTLA-4 (n=3, 15%). The median number of ICI cycles and median time from ICI initiation to onset of irNeuropathy symptoms were 2.5 cycles (range 1–20) and 9 weeks (range 1–56), respectively. ICIs were discontinued for all patients after diagnosis of irNeuropathy. Two non-neuroendocrine patients were restarted on different type of ICIs after irNeuropathy had resolved; one of these patients developed recurrent ICI-related phrenic neuropathy.

Neuroendocrine tumour associated irNeuropathies

All neuroendocrine tumour patients (small cell lung cancer, n=3; Merkel cell cancer, n=1) with irNeuropathies were seropositive for onconeural antibodies (type 1 antineuronal nuclear antibody (ANNA1, anti-Hu), n=2; ANNA1 and collapsin response …

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  • Contributors PC and DD conceptualised the study. PC carried major role in acquisition of data, analysed the data and drafted the manuscript for intellectual content. AZ and SS contributed to acquisition of data. All coauthors (AZ, SS, MR, PJD, CJK, SJP, MM and DD) revised the manuscript for intellectual content. All authors gave final approval for the submitted article and take responsibility for the accuracy and integrity of this work.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests SJP has patent pending for MAP1B as a marker of neurological autoimmunity.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.