CAR-T 细胞治疗的中枢神经系统淋巴瘤患者中的神经毒性：来自法国眼脑淋巴瘤网络的研究

We retrospectively selected adult patients with isolated CNS relapse of B-cell lymphomas treated with CAR T cells at Piti -Salp tri re 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.

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.