Neurotoxicity in Patients With CNS Lymphomas Treated With CAR T-Cell Therapy: A Study From the French Oculo-Cerebral Lymphoma Network.

Background and objectives: Several recent studies have shown the promising efficacy of chimeric antigenic receptor (CAR) T cells in treating CNS lymphomas. However, data on neurotoxicity in this setting are limited. The objective of this study was to describe neurotoxicity in patients with CNS lymphoma treated with anti-CD19 CAR T cells and to identify risk factors.

Methods: We retrospectively selected adult patients with isolated CNS relapse of B-cell lymphomas treated with CAR T cells at Pitié-Salpêtrière Hospital between January 2020 and January 2024 from the French Oculo-Cerebral Lymphoma network database. We collected clinical, biological, and imaging data before and after CAR T-cell infusion to investigate neurotoxicity. We considered only neurologic deterioration for which causes other than CAR T-cell toxicity were reasonably ruled out.

Results: According to the selection criteria, 48 patients (44% female, 28 with primary and 20 with secondary CNS lymphomas) were analyzed. The median age was 62 years (range: 30-82) at the time of CAR T-cell infusion, and the median Montreal Cognitive Assessment (MoCA) score was 23. Twenty-five patients received tisa-cel, 21 received axi-cel, and 2 received brexu-cel. Thirty-one patients (65%) experienced neurotoxicity, including 11 patients with grade 3-4 neurotoxicity (23%). The symptoms started at a median of 5 days (range: 1-10) after CAR T-cell infusion. The symptoms were cognitive disorders (N = 30), balance disorders (N = 18), consciousness disorders (N = 6), tremors (N = 6), seizures (N = 4), and motor deficits (N = 4). Brain MRI revealed pseudoprogression in 7 of 26 patients (27%), and there was a transient increase in CSF IL-10 levels in 7 of 29 patients (24%). Age 65 years or older (p = 0.04, OR: 4.4 [95% CI 1.1-19.3]) and a MoCA score <26 at the time of CAR T-cell infusion (p = 0.04, OR: 12 [95% CI 4-29]) were significantly associated with a greater risk of grade 3-4 neurotoxicity (exploratory analysis). Twenty patients (42%) received steroids. The median duration of neurologic impairment was 100 days (range: 4 days-18 months) in patients with grade 3-4 neurotoxicity.

Discussion: Although the rate of neurotoxicity seems acceptable in CNS lymphomas, the risk of unusual prolonged neurologic deterioration is high in patients with grade 3-4 neurotoxicity. Special attention should be given to older patients with cognitive impairment who seem at greater risk of severe forms of neurotoxicity. Larger series are warranted to confirm these results.