Seizure Prophylaxis in CAR T-Cell Therapy

Introduction to Seizure Prophylaxis

For patients receiving CAR T-cell therapy with CNS disease or history of seizures, levetiracetam is preferred over lacosamide for seizure prophylaxis, as recommended by the American Society of Clinical Oncology 1

Lacosamide is generally well-tolerated and can be used as adjunctive therapy for partial-onset seizures in adults with epilepsy, with or without secondary generalization, as recommended by the American Academy of Neurology 2, 3
Elderly patients may be more susceptible to side effects, particularly cardiac effects, and patients with renal impairment are at higher risk of adverse effects, including cardiac conduction abnormalities 3

Lacosamide works through a unique mechanism, selectively enhancing slow inactivation of voltage-gated sodium channels, stabilizing hyperexcitable neuronal membranes, and inhibiting neuronal firing, with a potential interaction with collapsin-response mediator protein 2 (CRMP-2) 4
The recommended dose range for lacosamide is 200-400mg per day, administered twice daily, with bioequivalence established between oral tablet and oral syrup formulations 4

Clinical trials have demonstrated significant efficacy as adjunctive therapy, with 34% of patients achieving ≥50% reduction in seizure frequency at 200mg/day and 40% at 400mg/day, compared to 23% with placebo 4
The most common side effects of lacosamide include central nervous system effects, visual disturbances, gastrointestinal effects, and administration-related effects 2, 3
Lacosamide has dose-dependent effects on cardiac conduction, including PR interval prolongation and a risk of atrioventricular block, particularly in elderly patients, patients with pre-existing cardiac conduction disorders, patients taking other medications that affect cardiac conduction, and patients with renal impairment 3

The American Heart Association and other guideline societies recommend baseline ECG and periodic cardiac assessment for patients taking lacosamide, especially those with known cardiac conduction problems or taking other medications that affect cardiac conduction, as well as mental health monitoring for signs of depression or suicidal ideation 3
Patients should be counseled on the potential effects of lacosamide on driving performance, as suggested by the American Academy of Neurology 4, 2
Lacosamide has a lower incidence of arousal-related adverse events compared to carbamazepine, and does not induce or inhibit cytochrome P450 enzymes, resulting in fewer drug-drug interactions than older antiseizure medications 3

Lacosamide is classified as a Schedule V controlled substance in the United States and is FDA-approved for adjunctive therapy for partial-onset seizures in adults with epilepsy, with or without secondary generalization, and is available in both oral and intravenous formulations 4
Despite studies in painful diabetic peripheral neuropathy (DPN), lacosamide was not approved for this indication by either the FDA or European Medicines Agency, as recommended by the European Medicines Agency 4