To evaluate clinical presentations and serological associations of immune checkpoint inhibitor (ICI) related neuropathy (irNeuropathy).

ICI indications have increased in the last few years, including their broad application in neuroendocrine tumor treatment.   

Patients with irNeuropathies were identified by electronic medical record search (01/01/2015 to 10/10/2020). Clinical presentations, electrodiagnostic features, autoantibody profiles and clinical outcomes were reviewed.

We identified 19 irNeuropathy patients evaluated at our institution. Underlying malignancies included melanoma (n=9), renal cell carcinoma (n=3), lung/gastro-intestinal/breast adenocarcinoma (n=3), small cell lung cancer (n=2), Merkel cell caner (n=1) and mesothelioma (n=1). Most common neuropathy phenotype was polyradiculoneuropathy/radiculoplexus neuropathy (n=8), followed by length-dependent peripheral neuropathy (n=6), unilateral/bilateral phrenic neuropathies (n=3) and brachial plexopathy (n=2). Six patients had evidence of demyelination on electrodiagnostic studies. All neuroendocrine tumor patients (small cell lung cancer, n=2; merkel cell cancer, n=1) with irNeuropathies were seropositive for onconeural antibodies (ANNA1 [anti-Hu], n=2; ANNA1 and CRMP5, n=1). These patients had mild neuropathic signs/symptoms (sensory ataxia or gastro-intestinal dysmotility) concerning for paraneoplastic neurological syndrome prior to ICI initiation. irNeuropathy outcomes were significantly worse in patients with neuroendocrine tumors versus non-neuroendocrine including modified Rankin scale ≥3 at nadir (100% vs 37.5%, p 0.047), Inflammatory Neuropathy Cause and Treatment disability score (median: 10 vs 2.5, p=0.013) and wheel chair dependence (100% vs 18.75%, p=0.005). Two of three neuroendocrine tumor patients with irNeuropathy died due to progressive neurological deterioration.