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@ARTICLE{Frenking:293957,
      author       = {J. H. Frenking$^*$ and X. Zhou and V. Wagner and T.
                      Hielscher$^*$ and J. Kauer and E. K. Mai and M. J. Friedrich
                      and C. S. Michel and M. Hajiyianni and I. Breitkreutz and P.
                      Costello and O. Nadeem and N. Weinhold$^*$ and H.
                      Goldschmidt and A. Schmitt and T. Luft and M. Schmitt and C.
                      Müller-Tidow and M. Topp and H. Einsele and P. Dreger and
                      N. C. Munshi and A. S. Sperling and L. Rasche and S. Sauer
                      and M.-S. Raab$^*$},
      title        = {{EASIX}-guided risk stratification for complications and
                      outcome after {CAR} {T}-cell therapy with ide-cel in
                      relapsed/refractory multiple myeloma.},
      journal      = {Journal for ImmunoTherapy of Cancer},
      volume       = {12},
      number       = {10},
      issn         = {2051-1426},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {DKFZ-2024-02022},
      pages        = {e009220},
      year         = {2024},
      note         = {#EA:A360#LA:A360#},
      abstract     = {Chimeric antigen receptor (CAR) T-cell therapy has
                      demonstrated significant benefits in the treatment of
                      relapsed/refractory multiple myeloma (RRMM). However, these
                      outcomes can be compromised by severe complications,
                      including cytokine release syndrome, immune effector
                      cell-associated neurotoxicity syndrome (ICANS) and immune
                      effector cell-associated hematotoxicity (ICAHT),
                      predisposing for life-threatening infections.This
                      retrospective observational study examined a total of 129
                      patients with RRMM who had received idecabtagene vicleucel
                      (ide-cel) at two major myeloma centers in Germany and one
                      center in the USA to assess the Endothelial Activation and
                      Stress Index (EASIX) as a risk marker for an unfavorable
                      clinical course and outcome after CAR T-cell therapy. EASIX
                      is calculated by lactate dehydrogenase (U/L) × creatinine
                      (mg/dL) / platelets (109 cells/L) and was determined before
                      lymphodepletion (baseline) and at the day of CAR T-cell
                      infusion (day 0). The analysis was extended to EASIX
                      derivatives and the CAR-HEMATOTOX score.An elevated baseline
                      EASIX (>median) was identified as a risk marker for severe
                      late ICAHT, manifesting with an impaired hematopoietic
                      reconstitution and pronounced cytopenias during the late
                      post-CAR-T period. Patients with high EASIX levels (>upper
                      quartile) were particularly at risk, as evidenced by an
                      increased rate of an aplastic phenotype of neutrophil
                      recovery, severe late-onset infections and ICANS. Finally,
                      we found associations between baseline EASIX and an inferior
                      progression-free and overall survival. Moreover, the EASIX
                      at day 0 also demonstrated potential to serve as a risk
                      marker for post-CAR-T complications and adverse outcomes.In
                      conclusion, EASIX aids in risk stratification at clinically
                      relevant time points prior to CAR T-cell therapy with
                      ide-cel. Increased EASIX levels might help clinicians to
                      identify vulnerable patients to adapt peri-CAR-T management
                      at an early stage.},
      keywords     = {Humans / Multiple Myeloma: therapy / Multiple Myeloma:
                      immunology / Male / Female / Middle Aged / Immunotherapy,
                      Adoptive: adverse effects / Immunotherapy, Adoptive: methods
                      / Aged / Retrospective Studies / Adult / Receptors, Chimeric
                      Antigen / Risk Assessment / Biological Products: therapeutic
                      use / Treatment Outcome / Cytokine Release Syndrome:
                      etiology / chimeric antigen receptor - CAR (Other) /
                      cytopenia (Other) / immunotherapy (Other) / multiple myeloma
                      (Other) / treatment related adverse event - trAE (Other) /
                      idecabtagene vicleucel (NLM Chemicals) / Receptors, Chimeric
                      Antigen (NLM Chemicals) / Biological Products (NLM
                      Chemicals)},
      cin          = {A360 / C060},
      ddc          = {610},
      cid          = {I:(DE-He78)A360-20160331 / I:(DE-He78)C060-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39379098},
      doi          = {10.1136/jitc-2024-009220},
      url          = {https://inrepo02.dkfz.de/record/293957},
}