Abstract Management of secondary central nervous system (SCNS) involvement in relapsed or refractory aggressive B-cell lymphomas remains an area of unmet medical need. We report a single-center retrospective analysis of 7 adult patients with SCNS lymphoma (SCNSL) who underwent chimeric antigen receptor (CAR) T-cell therapy for their refractory disease, and we describe the safety of whole brain radiation therapy (WBRT) as a bridging therapy. Six patients (85.7%) achieved a complete response at day 28, and 1 patient had progressive disease. The median progression-free survival was 83 days (range, 28-219 days), and median overall survival was 129 days (range, 32-219 days). Three patients died as a result of disease progression. Of the 5 patients who received WBRT as bridging therapy, 3 had no immune effector cell–associated neurotoxicity syndrome (ICANS), but 2 patients had grade 1 or grade 3 ICANS. No grade 4 ICANS was reported in this subset of patients. We conclude that SCNSL should not preclude patients from receiving CAR T-cell therapy as a treatment option because of concerns regarding ICANS, and bridging with WBRT is not associated with increased ICANS.