Home > Publications database > Clinical presentation, management, and outcome of TIAN in CNS lymphoma treated with CD19-CAR T-cell therapy. > print

001     305427
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100 1 _ |a Kaulen, Leon
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245 _ _ |a Clinical presentation, management, and outcome of TIAN in CNS lymphoma treated with CD19-CAR T-cell therapy.
260 _ _ |a Washington, DC
|c 2025
|b American Society of Hematology
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520 _ _ |a Tumor inflammation-associated neurotoxicity (TIAN) was recently proposed as a unique complication of immunotherapy in patients with brain tumor. Here, we report a first comprehensive characterization of TIAN in patients with central nervous system (CNS) lymphoma (CNSL) treated with CD19-directed chimeric antigen receptor (CD19-CAR) T cells. TIAN occurred in 10 of 56 (17.9%) patients with CNSL, with clinical onset at a median 3.5 days (range, 1-9) after CD19-CAR T-cell infusion. It was less frequently associated with cytokine release syndrome (60% vs 100%; P = .009) than immune effector cell-associated neurotoxicity syndrome (ICANS). Although symptoms were usually transient and fully reversible, TIAN was associated with a fatal outcome in 1 patient. Larger CNS tumor volume at baseline allowed the identification of patients at risk for TIAN (area under the curve, 0.847; P = .002). Maximizing Youden J statistics, a discriminatory tumor volume threshold of >3.4 cm3 was determined, which carried 87.5% sensitivity and 80.5% specificity. TIAN correlated with higher overall response rates to CD19-CAR T cells (90% vs 52%; P = .036) and improved progression-free survival (hazard ratio, 0.22; 95% confidence interval, 0.07-0.61; P = .006) on multivariate Cox proportional hazard regression. Postmortem histopathological evaluation of a TIAN lesion revealed a dense macrophage population with central necrosis and peripheral reactive gliosis, accompanied by loss of white matter and intracytoplasmic myelin in foamy macrophages. Collectively, our work supports TIAN as a localized on-tumor, on-target neurotoxicity syndrome, closely related to preexisting CNSL lesions and distinct from ICANS. CNS tumor volume at baseline may allow to identify patients at risk and may guide management.
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650 _ 7 |a Antigens, CD19
|2 NLM Chemicals
650 _ 7 |a Receptors, Chimeric Antigen
|2 NLM Chemicals
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Middle Aged
|2 MeSH
650 _ 2 |a Antigens, CD19: immunology
|2 MeSH
650 _ 2 |a Immunotherapy, Adoptive: adverse effects
|2 MeSH
650 _ 2 |a Central Nervous System Neoplasms: therapy
|2 MeSH
650 _ 2 |a Central Nervous System Neoplasms: immunology
|2 MeSH
650 _ 2 |a Central Nervous System Neoplasms: pathology
|2 MeSH
650 _ 2 |a Aged
|2 MeSH
650 _ 2 |a Adult
|2 MeSH
650 _ 2 |a Neurotoxicity Syndromes: etiology
|2 MeSH
650 _ 2 |a Neurotoxicity Syndromes: therapy
|2 MeSH
650 _ 2 |a Lymphoma: therapy
|2 MeSH
650 _ 2 |a Lymphoma: immunology
|2 MeSH
650 _ 2 |a Lymphoma: pathology
|2 MeSH
650 _ 2 |a Receptors, Chimeric Antigen: immunology
|2 MeSH
650 _ 2 |a Treatment Outcome
|2 MeSH
650 _ 2 |a Cytokine Release Syndrome: etiology
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700 1 _ |a Martinez-Lage, Maria
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700 1 _ |a Abramson, Jeremy S
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700 1 _ |a Karschnia, Philipp
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700 1 _ |a Doubrovinskaia, Sofia
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700 1 _ |a Shankar, Ganesh M
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700 1 _ |a Choi, Bryan D
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700 1 _ |a Ramundo, Christopher M
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700 1 _ |a Ehret, Felix
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700 1 _ |a Barnes, Jeffrey A
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700 1 _ |a El-Jawahri, Areej
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700 1 _ |a Hochberg, Ephraim P
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700 1 _ |a Johnson, P Connor
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700 1 _ |a Soumerai, Jacob D
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700 1 _ |a Plotkin, Scott R
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700 1 _ |a Batchelor, Tracy T
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700 1 _ |a Wick, Wolfgang
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700 1 _ |a Maus, Marcela V
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700 1 _ |a Chen, Yi-Bin
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700 1 _ |a Frigault, Matthew J
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700 1 _ |a Dietrich, Jorg
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