Neurologic - bmshkmedinfo

Management guidelines for neurologic irAEs

Common neurologic irAE symptoms

Encephalitis

Aseptic meningitis

Guillain-Barré syndrome

Myasthenia gravis

Peripheral neuropathy

Transverse myelitis

International guideline (ASCO, ESMO and NCCN) recommendations for neurologic irAEs^1–3 ^{^}

^{^} For detailed guidelines, please refer to original publication

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Grading	NCCN²	ASCO³
Grade 1 Mild symptoms, no interference with function	Consider holding immunotherapy Monitor symptoms for 1 week Consider B12, HgbA1c, SPEP with immunofixation, HIV, and ANCA Consider neuraxial imaging Evaluate for other causes of neuropathy	Consider holding immunotherapy Monitor closely for symptom progression Consider neurology consultation Serum testing Consider additional testing guided by neuropathy phenotype Consider spine MRI with/without contrast
Grade 2 Some interference with ADLs, symptoms concerning to the patient such as pain but no weakness or gait limitation	Hold immunotherapy Initial observation or initiate oral prednisone 0.5–1 mg/kg If progression, initiate IV methylprednisolone 2–4 mg/kg/day and manage as GBS Administer gabapentin, pregabalin, or duloxetine for pain B12, HgbA1c, SPEP with immunofixation, HIV, and ANCA Neuraxial imaging Consider EMG/NCS Consider neurology consultation Evaluate for other causes of neuropathy	Hold immunotherapy Initial observation or initiate prednisone 0.5–1 mg/kg/day if progressing from mild Administer gabapentin, pregabalin, or duloxetine for pain In addition to recommended testing for grade 1: MRI for spine, brain and plexus (if concern for plexus involvement) Consider lumbar puncture
Grade 3–4 Limiting self-care and aids warranted, weakness limiting walking or respiratory problems	Treat as GBS	Discontinue immunotherapy Admit patient Neurology consultation Initiate IV methylprednisolone 2–4 mg/kg/day and manage as GBS

*ESMO does not provide guidelines for specific neurologic adverse events. Please see the specific guidelines to view their general recommendations.

ADLs, activities of daily living; ANCA, antineutrophil cytoplasmic antibodies; ASCO, American Society of Clinical Oncology; EMG, electromyography; ESMO, European Society for Medical Oncology; GBS, Guillain-Barré syndrome; HgbA1c, haemoglobin A1c; HIV, human immunodeficiency virus; IV, intravenous; MRI, magnetic resonance imaging; NCCN, National Comprehensive Cancer Network; NCS, nerve conduction studies; SPEP, serum protein electrophoresis.

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ASCO³
Grading		Management
Grade 1	Mild symptoms, no interference with function and symptoms not concerning to patient	Consider holding immunotherapy Monitor closely
Grade 2	Moderate symptoms, some interference with ADLs, symptoms concerning to patient	Hold immunotherapy Initial observation or initiate prednisone 0.5–1 mg/kg/day Neurology consultation
Grade 3–4	Severe symptoms. Limiting self-care and aids warranted	Discontinue immunotherapy Admit patient Initiate methylprednisolone 1 g daily for 3 days followed by oral steroid taper Neurology consultation

*ESMO does not provide guidelines for specific neurologic adverse events. Please see the specific guidelines to view their general recommendations.

ADLs, activities of daily living; ASCO, American Society of Clinical Oncology; ESMO, European Society for Medical Oncology.

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Grading	NCCN²	ASCO³
Grade 1 Mild symptoms, no interference with function and symptoms not concerning to patient	Hold immunotherapy Start prednisone 0.5–1 mg/kg/day Consider IV acyclovir Add bacterial coverage Rule out bacterial and viral infection Brain MRI Consider spine MRI Lumbar puncture Consider neurology consultation	Hold immunotherapy Consider neurology consultation Consider IV acyclovir and antibacterial therapy Once bacterial and viral infection negative, consider close monitoring, oral prednisone 0.5–1 mg/kg/day, or IV methylprednisolone 1 mg/kg/day or if presenting moderate or severe symptoms Consider hospitalisation for Grade 3–4 Brain MRI with or without contrast Morning cortisol, ACTH to rule out adrenal insufficiency Strongly consider lumbar puncture with CSF analysis
Grade 2 Moderate symptoms, some interference with ADLs, symptoms concerning to patient
Grade 3–4 Severe symptoms, limiting self-care and aids warranted	Consider discontinuing immunotherapy Inpatient care Consider IV methylprednisolone 1–2 mg/kg/day Tests as described in Grade 1 and 2

*ESMO does not provide guidelines for specific neurologic adverse events. Please see the specific guidelines to view their general recommendations.

ACTH, adrenocorticotropic hormone; ADLs, activities of daily living; ASCO, American Society of Clinical Oncology; CSF, cerebrospinal fluid; ESMO, European Society for Medical Oncology; IV, intravenous; MRI, magnetic resonance imaging; NCCN, National Comprehensive Cancer Network.

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Grading	NCCN²	ASCO³
Grade 1 Mild symptoms, no interference with function and symptoms not concerning to patient³	Hold immunotherapy if mild Discontinue immunotherapy if severe Consider IV acyclovir Add bacterial coverage Trial of methylprednisolone 1–2 mg/kg/day, taper over 4 weeks once symptoms resolve If severe or progressing symptoms, strongly consider IV methylprednisolone 1 g daily for 3–5 days plus IVIG (10 mg/kg) or plasmapheresis If positive for autoimmune encephalopathy antibody or limited to no improvement, consider rituximab Inpatient care for Grade 3–4 Neurology consultation Brain MRI with and without contrast Consider spine MRI Lumbar puncture EEG ESR, CRP, ANCA (if vasculitic process suspected) CSF and serum studies	Hold immunotherapy Consider concurrent IV acyclovir Trial of methylprednisolone 1–2 mg/kg/day Consider pulse corticosteroids (methylprednisolone 1 g daily for 3–5 days plus IVIG 0.4 g/kg/day or plasmapheresis) Taper steroids following acute management over at least 4–6 weeks If positive for autoimmune encephalopathy or paraneoplastic antibody or limited to no improvement, consider rituximab Consider hospitalisation for Grade 3–4 Neurology consultation Brain MRI with/without contrast Lumbar puncture Serum studies EEG
Grade 2 Moderate symptoms, some interference with ADLs, symptoms concerning to patient³
Grade 3–4 Severe symptoms, limiting self-care and aids warranted³

*ESMO does not provide guidelines for specific neurologic adverse events. Please see the specific guidelines to view their general recommendations.

ADLs, activities of daily living; ANCA, anti-neutrophil cytoplasmic antibodies; ASCO, American Society of Clinical Oncology; CRP, C-reactive protein; CSF, cerebrospinal fluid; EEG, electroencephalogram; ESMO, European Society for Medical Oncology; ESR, erythrocyte sedimentation rate; IV, intravenous; IVIG, intravenous immunoglobulin; MRI, magnetic resonance imaging; NCCN, National Comprehensive Cancer Network.

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Grading	Management	Assessment
Grade 1 Asymptomatic or mild symptoms; clinical or diagnostic observations only	Continue immunotherapy Intervention not indicated	Neurology consultation Ophthalmic or neuro-ophthalmic evaluation if ocular involvement MRI with contrast of brain, orbit, cervical and thoracic spinal cord Lumbar puncture with CSF analysis and viral PCRs Serum studies Evaluation for urinary retention and constipation EEG
Grade 2 Moderate symptoms, minimal, limiting age-appropriate instrument ADL	Hold immunotherapy Neurology consultation Start prednisone 1 mg/kg daily and taper over 1 month Rule out infection
Grade 3 Severe or medically significant symptoms, limiting self-care ADL	Discontinue immunotherapy Neurology consultation Nonopioid management of neuropathic pain such as pregabalin, gabapentin or duloxetine Admit patient for methylprednisolone pulse dosing (1 g/day) Consider IVIG (2 g/kg in divided doses) or plasmapheresis if no improvement or symptoms worsen after 3 day
Grade 4 Life threatening consequences	Discontinue immunotherapy Neurology consultation ICU level inpatient care Start methylprednisolone pulse dosing (1 g/day) Consider IVIG (2 g/kg in divided doses) or plasmapheresis if no improvement or symptoms worsen after 3 days

ADL, activities of daily living; CSF, cerebrospinal fluid; EEG, electroencephalogram. ICU, intensive care unit; IVIG, intravenous immunoglobulin; MRI, magnetic resonance imaging; PCR, polymerase chain reaction.

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Diagnosis	Assessment and Management
Acute or subacute weakness or sensory changes bilaterally, often with bowel/bladder changes and spinal level to pinprick, hyperreflexia, positive Babinski	Discontinue immunotherapy Inpatient care IV methylprednisolone 1 g/day for 3–5 days, tapered over 4 weeks once symptoms resolve Neurology consultation MRI of the spine and brain with and without contrast Lumbar puncture Serum studies Bladder scan to evaluate constipation and urinary retention

*No grading for transverse myelitis provided in NCCN guidelines.
IV, intravenous; MRI, magnetic resonance imaging; NCCN, National Comprehensive Cancer Network.

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	NCCN²	ASCO³
Assessment	Neurology consultation Test for AChR, MuSK, and antistriational antibodies Pulmonary function assessment with NIF and VC Evaluate for concomitant myocarditis and myositis EMG/nerve conduction study Consider MRI Consider paraneoplastic workup Assess ESR and CRP
Grade 2 Some symptoms interfering with ADLs MGFA severity class I and II	Discontinue immunotherapy Low-dose oral prednisone (20 mg daily) Increase every 3–5 days to a target dose of 1 mg/kg/day but no more than 100 mg daily	Hold immunotherapy Administer corticosteroids (oral prednisone 0.5 mg/kg)

	Strongly consider inpatient care Pyridostigmine (initiate at 30 mg orally three times a day and increase to maximum of 120 mg orally four times a day).
Grade 3–4 Limiting self-care and aids warranted, weakness limiting walking, any dysphagia, facial weakness, respiratory muscle weakness, or rapidly progressive symptoms MGFA severity class III–IV	Permanently discontinue immunotherapy Admit patient (consider ICU-level monitoring) Initiate IVIG 0.4 g/kg/day IV over 5 days or plasmapheresis for 5 days Consider rituximab if refractory to IVIG or plasmapheresis Frequent pulmonary function assessment Daily neurologic review Avoid medication that can worsen myasthenia
	Administer IV methylprednisolone 1–2 mg/kg/day	Continue steroids, taper should begin 3–4 weeks after initiation Continue following Grade 2 recommendations

*ESMO does not provide guidelines for specific neurologic adverse events. Please see the specific guidelines to view their general recommendations.

AChR, acetylcholine receptor; ADLs, activities of daily living; ASCO, American Society of Clinical Oncology; CRP, C-reactive protein; EMG, electromyography; ESMO, European Society for Medical Oncology; ESR, erythrocyte sedimentation rate; ICU, intensive care unit; IV, intravenous; IVIG, intravenous immunoglobulin; MGFA, Myasthenia Gravis Foundation of America; MuSK, muscle-specific kinase; NCCN, National Comprehensive Cancer Network; NIF, negative inspiratory force; VC, vital capacity.

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	NCCN² and ASCO³
Assessment	Neurology consultation MRI of the spine with and without contrast Lumbar puncture with CSF analysis Serum antiganglioside antibody tests for GBS and its subtypes Consider paraneoplastic workup Pulmonary function testing (NIF or VC) Electrodiagnostic studies (NCS and EMG) to evaluate polyneuropathy Flow cytometry for those with haematologic malignancies ³
Grade 2 Moderate symptoms, some interference with ADLs, symptoms concerning to patient	Discontinue immunotherapy Inpatient care with access to ICU-level monitoring Start IVIG (2g/kg) or plasmapheresis in addition to IV methylprednisolone 1 gram daily for 5 days for severe cases, then taper over 4 weeks^† Frequent neurologic evaluation and pulmonary function monitoring Monitor for concurrent autonomic dysfunction Gabapentin, pregabalin, or duloxetine for pain management
Grade 3–4 Limiting self-care and aids warranted, weakness limiting walking, any dysphagia, facial weakness, respiratory muscle weakness, or rapidly progressive symptoms

*ESMO does not provide guidelines for specific neurologic adverse events. Please see the specific guidelines to view their general recommendations.

^†Corticosteroids are typically not recommended for idiopathic GBS, but a trial is reasonable for ICPi-related forms.

ADLs, activities of daily living; ASCO, American Society of Clinical Oncology; CSF, cerebrospinal fluid; EMG, electromyography; ESMO, European Society for Medical Oncology; GBS, Guillain-Barré syndrome; ICPi, immune checkpoint inhibitor; ICU, intensive care unit; IV, intravenous; IVIG, intravenous immunoglobulin; MRI, magnetic resonance imaging; NCCN, National Comprehensive Cancer Network; NCS, nerve conduction studies; NIF, negative inspiratory force; VC, vital capacity.

References:

Haanen J, et al. Ann Oncol 2022;33:1217–1238. Available at: https://www.annalsofoncology.org/article/S0923-7534(22)04187-4/fulltext. Accessed March 2025.
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Management of immunotherapy-Related Toxicities. Version 1.2022. Available at: https://www.nccn.org/professionals/physician_gls/pdf/immunotherapy.pdf. Accessed 13 February 2025.
Schneider BJ, et al. J Clin Oncol 2021;39:4073–4126. Available at: https://ascopubs.org/doi/full/10.1200/JCO.21.01440. Accessed March 2025.
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A. Peripheral neuropathy

Grading and management 2,3*

B. Autonomic neuropathy

Grading and management 3*

C. Aseptic meningitis

Grading and management 2,3*

D. Encephalitis

Management 2,3*

E. Transverse myelitis

ASCO grading and management 3

NCCN: assessment and management 2*

F. Myasthenia gravis

Grading and management 2,3*

G. Guillain-Barré syndrome

Management 2,3*