Acute Symptomatic Seizures During CAR T-Cell Therapy for Hematologic Malignancies: Tri-Site Mayo Clinic Experience.

Abstract

BACKGROUND AND OBJECTIVES Chimeric antigen receptor T-cell (CAR T-cell) therapy is associated with neurotoxicity, which may include acute symptomatic seizures (ASySs). Specific risk factors and short-term and long-term outcomes of ASyS associated with CAR T-cell therapy have not been well investigated. METHODS This retrospective cohort study evaluated incidence and risk factors for ASyS during CAR T-cell therapy. We included patients treated at Mayo Clinic in Minnesota, Florida, and Arizona who underwent CAR T-cell therapy for hematologic malignancies from October 2019 to November 2023. Pretreatment demographics, clinical information, type of CAR T-cell therapy, neuroimaging, laboratories during treatment, and clinical features during admission were analyzed. Data on treatment and prevalence of seizures, EEG, and survival at the last follow-up were assessed. T-tests and nonparametric testing were performed on categorical and continuous data, respectively. Multivariable analysis was also performed. RESULTS We included 180 patients (mean age 62.3 years, 57.2% women) with 8 (4.4%) developing ASyS at a mean of 8.0 ± 5.3 days after therapy. Earlier onset of cytotoxic release syndrome (odds ratio [OR] 1.81, 95% CI 0.62-2.99, p = 0.007), higher grade immune effector cell-associated neurotoxicity syndrome (ICANS) (OR -1.43, 95% CI -1.86 to -1.00, p < 0.001), focal neurologic deficits (OR 7.15, 95% CI 1.60-32.14, p = 0.007), and cefepime (OR 0.58, 95% CI 0.51-0.65, p = 0.022) exposure were significantly associated with a higher risk of ASyS. A multivariable model accounting for age and sex fit best using the lowest minimum immune effector cell encephalopathy score and highest ICANS grade (R2 = 0.555, χ2 = 28.507, p < 0.001). ASyS was associated with death at the last follow-up (OR 0.48, 95% CI 0.41-0.56, p = 0.007), although short-term outcomes were not affected by ASyS. Nonprotocolized antiseizure medication (ASM) prophylaxis did not affect ASyS incidence. DISCUSSION This study suggests a low risk of ASyS because of CAR T-cell therapy, with certain risk factors that may be predictive of ASyS and lack of a definitive and direct association of ASyS with outcomes. The current approach to ASM prophylaxis should be reconsidered when ICANS is encountered. This study is limited by its retrospective nature and the use of ASM prophylaxis in all patients with ICANS, which requires further study to assess its necessity.