Long-term treatment outcomes of immune checkpoint inhibitor-related neuropathies: a French multicenter cohort study

Current guidelines for immune-related neurotoxicities recommend discontinuation of immune checkpoint inhibitors (ICIs) and steroid therapy in severe cases. However, the management of ICI-related neuropathies remains less standardised, with intravenous immunoglobulin (IVIg) frequently combined with steroids despite limited evidence. This study aims to evaluate the treatment responses to immune-modulatory treatments in a multicenter French cohort of patients with ICI-related neuropathies. We conducted a retrospective analysis of patients with ICI-related neuropathies from six French centers. Clinical, biological and electrophysiological data were collected at baseline, 3 months, and 6 months. Patients were classified into three groups based on neuropathy type: demyelinating, axonal, or multiradiculopathic. The outcome was defined by changes in the modified Rankin Scale (mRS) and the Inflammatory Neuropathy Cause and Treatment (INCAT) disability scores between baseline and follow-up visits. Forty-eight patients with ICI-related neuropathies were identified including 24 demyelinating neuropathies, 18 axonal neuropathies, and 6 multifocal radiculopathies. Most presented with subacute onset and predominant sensory symptoms. ICIs were discontinued in all patients, and immunomodulatory therapy was initiated for severe cases, primarily steroids alone (n = 25) or steroids combined with IVIg (n = 14). Overall, 90% of patients achieved a favourable and rapid outcome: 11 experienced complete recovery, while 32 showed partial or subtotal improvement. No significant advantage was observed in adding IVIg to steroids when comparing the two treatment groups. In the analysis of other variables, a higher baseline disability score (INCAT) was the only factor significantly associated with poorer outcomes. The following variables did not significantly impact outcomes: neuropathy type, ICI class, treatment type, presence of antiganglioside antibodies, or time to ICI discontinuation and steroid initiation. ICIs were reintroduced in eleven patients, with good tolerance observed. Although limited by its retrospective design, this study did not demonstrate a clear added benefit of IVIg when combined with steroids as first-line treatment for ICI-related neuropathies. Reintroduction of ICIs after resolution of neurological impairment appears safe and feasible.