Neurological adverse events of ICI therapy: A ten-year comprehensive management from a multidisciplinary team.

Background: The unique mechanism of action of immune checkpoint inhibitors (ICI) can lead to auto-inflammatory events, potentially involving any organ. Among those, different rare immune related adverse events (irAEs) have also been identified, with Neurological irAEs (NirAEs) accounting for 1-5 %. In this scenario, we here report the 10-year experience of the multidisciplinary team at the University Hospital of Siena, Italy, in the diagnosis and clinical management of NirAEs.

Methods: A case series of ICI-treated patients with clinical suspect of Nir-AEs were evaluated by an experienced neurologist team. Neurological specific antibodies were tested in central/peripheral toxicities. In case of suspicious of CNS NirAEs, lumbar puncture was utilized to exclude infectious/paraneoplastic causes. In patients with signs and symptoms suggestive for myositis, a diagnostic muscular biopsy was performed.

Results: From January 2012 to December 2022, 1328 patients with solid tumors were treated with ICI, and 24 (1,8 %) were diagnosed with NirAEs: peripheral, central, or both in 20, 1, and 3 cases respectively. The most representative neurotoxicity was muscular/neuromuscular junction involvement. Histological examination of muscle biopsies depicted two main pathological patterns: highly inflammatory or necrotizing. NirAEs were Grade (G) 1-2 (11), G3-4 (10), G5 (3) and were treated with steroids, immunoglobulins and/or plasma exchange. Treatment led to complete or partial recovery of NirAEs in 11 (46 %) and 10 patients (42 %), respectively. In 3 cases NirAEs progressively worsened and patients died thereafter.

Conclusions: Our long-term experience indicates that a multidisciplinary approach avoids worsening of NirAEs leading to clinical recovery in the large majority of ICI-treated patients.