Comparison of immune checkpoint inhibitor-related neuropathies among patients with neuroendocrine and non-neuroendocrine tumours

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 …