Immune checkpoint inhibitors (ICIs) are associated with various neurological adverse events (NAEs). We herein explored the incidence and clinical phenotype of immune‐related NAEs in cancer patients. Medical records of ICI‐treated cancer patients were reviewed between the years 2010 and 2018, with an aim to characterize immuno‐related NAEs. A total of 1185 ICIs‐treated patients were identified, 63.7% of which were males and 36.3% were females, with a mean age of 63.4 ± 7.3 years. Twenty‐four from the overall ICIs‐treated patients (2%) developed NAEs. No differences were identified in terms of age, sex, tumor type and class of ICIs between the patients who developed NAEs and those who did not. The median number of cycles of ICI treatment before NAEs onset were 4.5 (1‐10), and the median time was 102 days. Peripheral nervous system (PNS) involvement was present in 14 patients (58.4%) and central nervous system (CNS) involvement in 10 (33.3%), including 2 patients with aseptic meningitis and polyradicular involvement. Amongst PNS complications, there were five (20.8%) with axonal sensory neuropathies, four (16.7%) with Guillain‐Barre‐like syndromes, and four (16.7%) with myositis and/or myasthenic syndromes. The majority of patients with PNS‐related NAEs (n = 11; 78.6%) improved after ICIs discontinuation and treatment with immune‐modulating therapies. The time to neuromuscular toxicities onset was significantly shorter, compared to CNS NAEs (median 70 vs 119 days, P = .037). Immune‐related NAEs mostly present with neuromuscular complications. Discontinuation of ICIs and appropriate treatment should be commenced early throughout the process, in order to maximize a favorable outcome.

Over the last decade, immune checkpoint inhibitors (ICIs) have revolutionized the treatment of several cancer types. ICIs work through the blockage of immune inhibitory signals, while increasing the T-cell specific immune antitumoral response. However, due to the fact that ICIs’ mechanism of action is not tissue antigen-specific and not limited to the tumor microenvironment, the use of cancer immunotherapy can produce a broad range of immune-related adverse events (irAEs). Neurological immune-related adverse events (NirAEs) are rare (the overall incidence varies between 1% to 6%), and these adverse events mainly concern the peripheral nervous system, rather than the central nervous system. Due to their potential severity, which could cause interruptions to cancer treatment, NirAEs are of particular clinical importance. Currently, the pathogenesis of these complications is not completely understood, although T-cells seem to play a principal role. Nevertheless, the development of NirAEs is likely to be a multifactorial and complex process. This conclusion can be extracted from the wide range of neurological auto-inflammatory and autoimmune disorders triggered or exacerbated by ICIs, and the extensive variability of the limited histological findings reported. The aim of this review is to summarize the potential immune-driven pathological mechanisms of NirAEs.

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Thus far, there are conflicting results on the causal role of K+ channels in the pathogenesis of acute oxaliplatin‐induced peripheral neurotoxicity (OXAIPN). As such, we tested the hypothesis that the voltage‐gated K+ channel KCNN3 repeat polymorphism confers liability to acute OXAIPN. DNA from 151 oxaliplatin‐treated patients for colorectal cancer was extracted and genotyped. The incidence of acute OXIPN was measured by the OXA‐neuropathy questionnaire, while the severity of acute OXAIPN was scored basing on the number of symptoms reported by the patients at each clinical assessment. The increased number of acute symptoms was considered as being suggestive of an increased severity of acute OXAIPN. A total of 130/151 (86.1%) patients developed any grade of acute OXAIPN. Grade I acute neurotoxicity was revealed in 43 (28.5%) patients; grade II in 34 (22.5%); and grade III in 53 (53.1%) patients. Genotyping revealed alleles carrying 11 to 20 CAG repeats. The majority of patients were heterozygous (131; 89.4%). The most common numbers of CAG repeats were 15 (n = 46), 16 (n = 53), and 17 (n = 95). Patients carrying alleles with either 15 to 17 CAG repeats (P = .601) did not experience a higher incidence of grade III (treatment‐emergent) acute OXAIPN. Likewise, no increased incidence of acute treatment‐emergent OXAIPN was noted in heterozygous patients carrying either two short alleles (<19 CAG repeats) or one short and one long (≥19 CAG repeats) allele (P = .701). Our results do not support a causal relationship between the KCNN3CAG repeat polymorphism and acute OXΑIPN.

We report the outcome of a pilot, open‐label study that tested the potential of lacosamide (200 mg/bi.d) as an effective and safe symptomatic treatment against acute painful oxaliplatin‐induced peripheral neurotoxicity (OXAIPN). Lacosamide was introduced in 18 colorectal cancer patients with evidence of clinically significant acute, painful OXAIPN after infusion of the third course (T1) of oxaliplatin‐based chemotherapy (FOLFOX4) and was maintained until completion of all 12 courses (T4). The OXA‐Neuropathy Questionnaire (OXA‐NQ) was used to record the severity of acute OXAIPN; the PI‐NRS estimated the severity of neuropathic pain, while the chronic OXAIPN was graded with TNSc. The EuroQOL (EQ‐5D) instrument was also applied. The Patient Global Impression of Change (PGIC) scale measured the lacosamide‐attributed perception of change. LCM‐responders were considered those with ≥50% reduction in PI‐NRS and OXA‐NQ scores at T4, compared to T1. Patients experienced on T1 a median number of acute OXAIPN symptoms of 4 and had a median neuropathic pain severity score of 6, which was strongly related to lower quality of life, according to EQ‐VAS (P < .001). At T4, 12 patients (66.7%) were classified as responders. A significant clinical improvement was documented in the severity of acute OXAIPN and neuropathic pain in relation to lacosamide (P < .001) at T4 compared to T1, which was associated with improved EQ‐VAS scores (P < .001). Twelve patients scored PGIC ≥5 (lacosamide‐attributed) at T4. There were no incidences of early drop‐outs for safety reasons. Lacosamide appears to be an effective and well‐tolerated symptomatic treatment against acute, painful OXAIPN.