Journal Article

DKFZ-2025-02156

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Clinical presentation, management, and outcome of TIAN in CNS lymphoma treated with CD19-CAR T-cell therapy.

Kaulen, L. (First author)DKFZ* ; Martinez-Lage, M. ; Abramson, J. S. ; Karschnia, P. ; Doubrovinskaia, S.DKFZ* ; Shankar, G. M. ; Choi, B. D. ; Ramundo, C. M. ; Ehret, F.DKFZ* ; Barnes, J. A. ; El-Jawahri, A. ; Hochberg, E. P. ; Johnson, P. C. ; Soumerai, J. D. ; Plotkin, S. R. ; Batchelor, T. T. ; Wick, W.DKFZ* ; Maus, M. V. ; Chen, Y.-B. ; Frigault, M. J. ; Dietrich, J.

2025
American Society of Hematology Washington, DC

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Please use a persistent id in citations: doi:10.1182/blood.2025028964

Abstract: 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.

Keyword(s): Humans (MeSH) ; Male (MeSH) ; Female (MeSH) ; Middle Aged (MeSH) ; Antigens, CD19: immunology (MeSH) ; Immunotherapy, Adoptive: adverse effects (MeSH) ; Central Nervous System Neoplasms: therapy (MeSH) ; Central Nervous System Neoplasms: immunology (MeSH) ; Central Nervous System Neoplasms: pathology (MeSH) ; Aged (MeSH) ; Adult (MeSH) ; Neurotoxicity Syndromes: etiology (MeSH) ; Neurotoxicity Syndromes: therapy (MeSH) ; Lymphoma: therapy (MeSH) ; Lymphoma: immunology (MeSH) ; Lymphoma: pathology (MeSH) ; Receptors, Chimeric Antigen: immunology (MeSH) ; Treatment Outcome (MeSH) ; Cytokine Release Syndrome: etiology (MeSH) ; Antigens, CD19 ; Receptors, Chimeric Antigen

Note: #EA:B320#

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Contributing Institute(s):

1. KKE Neuroonkologie (B320)
2. DKTK Koordinierungsstelle Berlin (BE01)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2025

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 20 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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