Neurotoxicity in Patients With CNS Lymphomas Treated With CAR T-Cell Therapy: A Study From the French Oculo-Cerebral Lymphoma NetworkHernández-Tost, Weiss, Choquet
et alNeurology (2025) 104 (8), e213501
Abstract: 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.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.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.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.
BCMA CAR-T therapy as salvage therapy in patients with plasmablastic myelomaJin, Deng, Jiang
et alHematology (2025) 30 (1), 2481555
Abstract: Plasmablastic myeloma (PBM) is a variant of multiple myeloma associated with a poor prognosis. We investigated the efficacy and safety of B-cell maturation antigen (BCMA) chimeric antigen receptor T cell (CAR-T) therapy in patients with PBM.The study comprised six patients diagnosed with PBM between January 1, 2023 and December 31, 2023. The patients received BCMA single-target CAR-T therapy or BMCA/CD19 dual-target CAR-T therapy, with some patients undergoing hematopoietic stem cell transplantation before treatment. The median patient age was 55.5 years (range, 41-63). Four patients exhibited high-risk cytogenetic abnormalities.The objective response rate (ORR) was 83.3%, with four of six patients achieving a complete response or better and three of six achieving a strigent complete response. Two patients exhibited progression-free survival (PFS) of at least 6 months, one of whom succumbed to a pulmonary infection, whereas four patients died of disease progression. Cytokine release syndrome (CRS) was observed in all patients, three of whom experienced grade 3-4 CRS. Two patients experienced grade 1-2 immune effector cell-associated neurotoxicity syndrome. There were no CRS-related deaths.BCMA CAR-T therapy was safe and effective as a salvage treatment for PBM, and its toxicity was controllable. Future research will examine the use of CAR-T therapy as part of combination regimens.
A comparison of Gam-COVID-Vac vaccination and non-vaccination on neurological symptoms and immune response in post-COVID-19 syndromeKurmangaliyeva, Madenbayeva, Urazayeva
et alQatar Med J (2025) 2025 (1), 6
Abstract: The post-COVID-19 syndrome may present with a range of neurological symptoms such as headaches, sleep disorders, and dizziness. The objective of this study was to examine the effectiveness of the Gam-COVID-Vac vaccine in mitigating the neurological symptoms of post-COVID-19 syndrome. The study involved 95 patients diagnosed with the neurological form of long COVID-19, who were divided into two groups according to their vaccination status. The immunological parameters of humoral immunity were evaluated by enzyme-linked immunosorbent assay (ELISA), while the parameters of cellular immunity were evaluated using flow cytometry. Administration of the vaccination resulted in a reduction in clinical symptoms of the neurological form of long COVID-19. Statistically significant differences (p = 0.035) were found in symptoms such as headaches, sleep disturbances, and dizziness, especially in central nervous system (CNS) disorders, between the groups that received the vaccination and those that did not. More than 90% of patients had elevated levels of Receptor Binding Domain (RBD) immunoglobulin G against the viral S-protein (>2,500 BAU/ml), indicating strong humoral immunity regardless of vaccination status. An increase in B-lymphocyte (CD3-CD19+) counts was noted in both groups, with levels significantly higher in the group that received the vaccination (p < 0.03). Analysis of T-cell profiles and NK (natural killer) cell levels showed no changes. The study suggests that administration of Gam-COVID-Vac vaccination could reduce the occurrence of CNS symptoms in individuals with post-COVID-19 syndrome. Although certain neurological symptoms may continue, immunization has a beneficial influence on their progression. The results emphasize the crucial role of an increased humoral immune response in individuals with post-COVID-19 syndrome, but do not show significant changes in T-cell immune parameters.© 2025 Kurmangaliyeva, Madenbayeva, Urazayeva, Baktikulova, Kurmangaliyev, licensee HBKU Press.
Early Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Infection Induces Necroptosis in Immune Cells of Peripheral Lymphoid OrgansXu, Huo, Yang
et alViruses (2025) 17 (3)
Abstract: The highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) has caused huge economic losses to the pig industry in China. This study evaluated the damage to peripheral immune tissues in the early infection of HP-PRRSV, including the hilar lymph nodes, mandibulares lymph nodes, inguinales superficials lymph nodes, spleens, and tonsils. HP-PRRSV infection led to a reduction in CD4+ and CD8+ T cells, as well as CD19+ B cells, in the tonsils. Additionally, CD163+ macrophages and CD56+ NK cells increased in all peripheral lymphoid organs, with NK cells migrating toward the lymphoid follicles. However, no significant changes were observed in CD11c+ dendritic cells. RNA-seq analysis showed the down-regulation of T and B cell functions, while macrophage and NK cell functions were enhanced. Gene Ontology (GO) and KEGG pathway analysis indicated the up-regulation of necroptosis processes. Western blotting and immunofluorescence confirmed that HP-PRRSV induced PKR-mediated necroptosis in immunocytes. This study provides new insights into the effects of early HP-PRRSV infection on peripheral immune organs, highlighting dynamic shifts in immune cell populations, virus-induced immunosuppression, and the role of PKR-mediated necroptosis. These findings improve our understanding of the immunomodulation induced by PRRSV infection.
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