Neurological Complications of Immune Checkpoint Inhibitors (P12-13.004)

Neurological Adverse Events Related to Immune Checkpoint Inhibitors: A Practical Review

“…(a) Timing is crucial for identifying n-irAEs, as they usually emerge within 3-6 months after initiating ICI treatment, with a median onset of 4 weeks (ranging from 1 to 85 weeks) [9,[22][23][24][25]. Neurological symptoms emerging beyond 6 months after the last ICI dose are less likely to be secondary to an irAE, although it cannot be entirely ruled out solely on this basis [8]; (b) Clinical and/or radiological evidence of cancer control coinciding with the onset of neurological symptoms supports n-irAE diagnosis rather than attributing the symptoms to cancer progression [22]; (c) The concurrent occurrence of neurological symptoms with other irAEs increases the likelihood of a n-irAE [11,22]; (d) A positive response to ICI interruption and/or immunosuppression also suggests a n-irAE, although it is not a definitive indicator [8].…”

“…These include a wide range of conditions, such as infections (viral or bacterial), cancer progression (including leptomeningeal carcinomatosis), metabolic issues (hypothyroidism, hypercalcemia), nutritional deficiencies, neurotoxicity from other treatments (e.g., platinum-induced sensory neuronopathy and cognitive side effects from radiotherapy), epilepsy, and vascular causes. Other features can help to suspect irAEs: Timing is crucial for identifying n-irAEs, as they usually emerge within 3–6 months after initiating ICI treatment, with a median onset of 4 weeks (ranging from 1 to 85 weeks) [ 9 , 22 , 23 , 24 , 25 ]. Neurological symptoms emerging beyond 6 months after the last ICI dose are less likely to be secondary to an irAE, although it cannot be entirely ruled out solely on this basis [ 8 ]; Clinical and/or radiological evidence of cancer control coinciding with the onset of neurological symptoms supports n-irAE diagnosis rather than attributing the symptoms to cancer progression [ 22 ]; The concurrent occurrence of neurological symptoms with other irAEs increases the likelihood of a n-irAE [ 11 , 22 ]; A positive response to ICI interruption and/or immunosuppression also suggests a n-irAE, although it is not a definitive indicator [ 8 ].…”

“…Timing is crucial for identifying n-irAEs, as they usually emerge within 3–6 months after initiating ICI treatment, with a median onset of 4 weeks (ranging from 1 to 85 weeks) [ 9 , 22 , 23 , 24 , 25 ]. Neurological symptoms emerging beyond 6 months after the last ICI dose are less likely to be secondary to an irAE, although it cannot be entirely ruled out solely on this basis [ 8 ];…”

“…A review of 59 studies, encompassing a total of 9,208 patients, revealed an incidence of n-irAEs reaching 3.8% with anti-CTLA4 therapy, 6.1% with anti-PD1 therapy, and 12% with combination therapy (i.e., anti-CTLA4 plus anti-PD1) [ 7 ]. However, this incidence is probably over- or under-estimated, as 55% of these n-irAEs consisted in non-specific symptoms, such as asthenia or headache and confusion, which are not included in a recent classification of n-irAEs [ 8 , 9 , 10 ]. Grade ≥ 3 n-irAEs represented less than 2% of these cases [ 11 ].…”