1. Neurotoxicity and management of primary and secondary central nervous system lymphoma after adoptive immunotherapy with CD19-directed chimeric antigen receptor T-cells.
- Author
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Karschnia P, Arrillaga-Romany IC, Eichler A, Forst DA, Gerstner E, Jordan JT, Ly I, Plotkin SR, Wang N, Martinez-Lage M, Winter SF, Tonn JC, Rejeski K, von Baumgarten L, Cahill DP, Nahed BV, Shankar GM, Abramson JS, Barnes JA, El-Jawahri A, Hochberg EP, Johnson PC, Soumerai JD, Takvorian RW, Chen YB, Frigault MJ, and Dietrich J
- Subjects
- Humans, Immunotherapy, Adoptive adverse effects, C-Reactive Protein, Retrospective Studies, Central Nervous System, T-Lymphocytes, Receptors, Chimeric Antigen, Lymphoma therapy, Central Nervous System Neoplasms therapy, Neurotoxicity Syndromes etiology, Neurotoxicity Syndromes therapy
- Abstract
Background: Chimeric antigen receptor (CAR) T-cells targeting CD19 have been established as a leading engineered T-cell therapy for B-cell lymphomas; however, data for patients with central nervous system (CNS) involvement are limited., Methods: We retrospectively report on CNS-specific toxicities, management, and CNS response of 45 consecutive CAR T-cell transfusions for patients with active CNS lymphoma at the Massachusetts General Hospital over a 5-year period., Results: Our cohort includes 17 patients with primary CNS lymphoma (PCNSL; 1 patient with 2 CAR T-cell transfusions) and 27 patients with secondary CNS lymphoma (SCNSL). Mild ICANS (grade 1-2) was observed after 19/45 transfusions (42.2%) and severe immune effector cell-associated neurotoxicity syndrome (ICANS) (grade 3-4) after 7/45 transfusions (15.6%). A larger increase in C-reactive protein (CRP) levels and higher rates of ICANS were detected in SCNSL. Early fever and baseline C-reactive protein levels were associated with ICANS occurrence. CNS response was seen in 31 cases (68.9%), including a complete response of CNS disease in 18 cases (40.0%) which lasted for a median of 11.4 ± 4.5 months. Dexamethasone dose at time of lymphodepletion (but not at or after CAR T-cell transfusion) was associated with an increased risk for CNS progression (hazard ratios [HR] per mg/d: 1.16, P = .031). If bridging therapy was warranted, the use of ibrutinib translated into favorable CNS-progression-free survival (5 vs. 1 month, HR 0.28, CI 0.1-0.7; P = .010)., Conclusions: CAR T-cells exhibit promising antitumor effects and a favorable safety profile in CNS lymphoma. Further evaluation of the role of bridging regimens and corticosteroids is warranted., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2023
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