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@ARTICLE{Kaulen:305427,
      author       = {L. Kaulen$^*$ and M. Martinez-Lage and J. S. Abramson and
                      P. Karschnia and S. Doubrovinskaia$^*$ and G. M. Shankar and
                      B. D. Choi and C. M. Ramundo and F. Ehret$^*$ and J. A.
                      Barnes and A. El-Jawahri and E. P. Hochberg and P. C.
                      Johnson and J. D. Soumerai and S. R. Plotkin and T. T.
                      Batchelor and W. Wick$^*$ and M. V. Maus and Y.-B. Chen and
                      M. J. Frigault and J. Dietrich},
      title        = {{C}linical presentation, management, and outcome of {TIAN}
                      in {CNS} lymphoma treated with {CD}19-{CAR} {T}-cell
                      therapy.},
      journal      = {Blood},
      volume       = {146},
      number       = {16},
      issn         = {0006-4971},
      address      = {Washington, DC},
      publisher    = {American Society of Hematology},
      reportid     = {DKFZ-2025-02156},
      pages        = {1902 - 1913},
      year         = {2025},
      note         = {#EA:B320#},
      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.},
      keywords     = {Humans / Male / Female / Middle Aged / Antigens, CD19:
                      immunology / Immunotherapy, Adoptive: adverse effects /
                      Central Nervous System Neoplasms: therapy / Central Nervous
                      System Neoplasms: immunology / Central Nervous System
                      Neoplasms: pathology / Aged / Adult / Neurotoxicity
                      Syndromes: etiology / Neurotoxicity Syndromes: therapy /
                      Lymphoma: therapy / Lymphoma: immunology / Lymphoma:
                      pathology / Receptors, Chimeric Antigen: immunology /
                      Treatment Outcome / Cytokine Release Syndrome: etiology /
                      Antigens, CD19 (NLM Chemicals) / Receptors, Chimeric Antigen
                      (NLM Chemicals)},
      cin          = {B320 / BE01},
      ddc          = {610},
      cid          = {I:(DE-He78)B320-20160331 / I:(DE-He78)BE01-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40663771},
      doi          = {10.1182/blood.2025028964},
      url          = {https://inrepo02.dkfz.de/record/305427},
}