Clinical presentation, management, and outcome of TIAN in CNS lymphoma treated with CD19-CAR T-cell therapy

Kaulen LD, Martinez-Lage M, Abramson JS, Karschnia P, Doubrovinskaia S, Shankar GM, Choi BD, Ramundo CM, Ehret F, Barnes JA, El-Jawahri A, Hochberg EP, Johnson PC, Soumerai JD, Plotkin SR, Batchelor TT, Wick W, Maus MV, Chen YB, Frigault MJ, Dietrich J (2025)


Publication Type: Journal article

Publication year: 2025

Journal

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.

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How to cite

APA:

Kaulen, L.D., Martinez-Lage, M., Abramson, J.S., Karschnia, P., Doubrovinskaia, S., Shankar, G.M.,... Dietrich, J. (2025). Clinical presentation, management, and outcome of TIAN in CNS lymphoma treated with CD19-CAR T-cell therapy. Blood. https://doi.org/10.1182/blood.2025028964

MLA:

Kaulen, Leon D., et al. "Clinical presentation, management, and outcome of TIAN in CNS lymphoma treated with CD19-CAR T-cell therapy." Blood (2025).

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