Management of Headaches in CAR-T Therapy Patients

Understanding Headache in the CAR-T Context

• Headaches occur commonly during CAR-T therapy, typically appearing within 2-7 days after infusion as part of CRS, or 4-10 days after infusion as part of ICANS, according to the National Comprehensive Cancer Network 1, 3
• The American Society for Transplantation and Cellular Therapy does not consider headache alone a useful diagnostic symptom for ICANS, as it is very common and frequently co-occurs with fever 1, 2
• Headaches are not included in the ASTCT ICANS consensus grading scale, though they may warrant careful attention and directed therapy, as recommended by the Journal of Clinical Oncology 4, 5

Supportive Management Algorithm

• The National Comprehensive Cancer Network recommends administering antipyretics for headache associated with fever, and providing IV hydration to maintain adequate perfusion 3, 6
• The Journal of Clinical Oncology suggests ensuring aspiration precautions and elevating the head of bed if any neurologic symptoms present, and avoiding medications that cause CNS depression 5, 7, 8

Monitoring Requirements

• The Journal of Clinical Oncology recommends performing neurologic evaluation, including ICE score assessment, at least twice daily during the high-risk period, and monitoring vital signs every 4-8 hours 7, 9, 10
• The National Comprehensive Cancer Network suggests checking daily laboratory tests, including CBC, CMP, CRP, and ferritin, for CRS surveillance 3, 6

When Headache Signals More Serious Toxicity

• The Journal of Clinical Oncology recommends obtaining brain MRI with and without contrast for Grade ≥2 ICANS, which includes any altered level of consciousness, confusion, or ICE score 3-6 4, 7
• The National Comprehensive Cancer Network suggests considering baseline brain imaging before CAR-T infusion in high-risk patients or those with pre-existing neurologic conditions 9, 10

Escalation Criteria

• The Journal of Clinical Oncology recommends initiating dexamethasone 10 mg IV and reassessing every 6-12 hours if no improvement for headache with ICE score 3-6, mild somnolence, or confusion (Grade 2 ICANS) 4, 5
• The Journal of Clinical Oncology suggests administering methylprednisolone 1,000 mg IV 1-2 times daily for 3 days for headache with severe altered consciousness, seizures, or focal neurologic deficits (Grade 3-4 ICANS) 4, 5

Seizure Prophylaxis Considerations

• The Journal of Clinical Oncology recommends considering levetiracetam 500-750 mg orally every 12 hours for 30 days starting on the day of infusion, especially for CAR-T products known to cause severe neurotoxicity 4, 9
• The Journal of Clinical Oncology suggests continuing prophylactic levetiracetam if EEG shows no seizure activity, and escalating treatment if non-convulsive status epilepticus is detected 8

Critical Management Pitfalls to Avoid

• The National Comprehensive Cancer Network recommends not routinely administering corticosteroids as pre-medication before CAR-T infusion, as this may mask early toxicity symptoms 10, 6
• The Journal of Clinical Oncology suggests not dismissing headache in the context of other neurologic symptoms, and always performing formal ICE score assessment 4, 5
• The Journal of Clinical Oncology recommends avoiding the use of tocilizumab for isolated ICANS symptoms, as it has not been shown to mitigate neurologic toxicity and may worsen ICANS 4, 5