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@ARTICLE{Biederstdt:303085,
      author       = {A. Biederstädt and F. Bassermann$^*$ and J. S. Hecker},
      title        = {{A}llogeneic {CAR}-engineered cellular therapy for relapsed
                      and refractory large {B} cell lymphoma: a systematic review
                      and meta-analysis.},
      journal      = {Frontiers in immunology},
      volume       = {16},
      issn         = {1664-3224},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {DKFZ-2025-01510},
      pages        = {1585556},
      year         = {2025},
      abstract     = {Relapsed/refractory (r/r) large B-cell lymphoma (LBCL)
                      remains a difficult-to-treat disease with limited treatment
                      options and high unmet clinical need, necessitating the
                      development of new therapies with greater potency and
                      broader applicability. While autologous chimeric antigen
                      receptor (CAR)-T cell therapies have transformed the
                      treatment landscape, $60-65\%$ of patients receiving these
                      therapies eventually relapse, underscoring the need for
                      improved approaches. Allogeneic CAR-T and CAR-NK cell
                      therapies have recently emerged as promising alternatives,
                      offering the potential to shorten manufacturing times,
                      reduce costs, and expand access to a broader patient
                      population. This systematic review and meta-analysis
                      compiles the currently available clinical trial data on the
                      efficacy and safety of these novel therapies in adult
                      patients with r/r LBCL.A systematic search of MEDLINE,
                      EMBASE, Web of Science, and the Cochrane Central Register of
                      Controlled Trials was conducted for studies published up to
                      January 12, 2025, involving allogeneic CAR-T and CAR-NK cell
                      therapies in R/R LBCL. The primary outcomes assessed were
                      the best overall response rate (bORR) and best complete
                      response rate (bCRR) at any time point. Secondary outcomes
                      included rates of grade 1-2 and grade 3+ cytokine release
                      syndrome (CRS), grade 1-2 and grade 3+ immune effector
                      cell-associated neurotoxicity syndrome (ICANS), grade 1-2
                      and grade 3+ infections and incidence of graft-versus-host
                      disease (GvHD).Nineteen studies met the inclusion and
                      exclusion criteria, encompassing 334 patients (155 CAR-NK;
                      179 CAR-T) evaluable for safety and 235 patients evaluable
                      for response (77 CAR-NK; 158 CAR-T). The pooled estimates
                      for the best overall response rate (bORR) and the best
                      complete response rate (bCRR) were $52.5\%$ $[95\%$ CI,
                      41.0-63.9] and $32.8\%$ $[95\%$ CI, 24.2-42.0],
                      respectively. Safety analysis revealed very low incidences
                      of grade 3+ CRS $(0.04\%$ $[95\%$ CI 0.00-0.49]) or grade 3+
                      ICANS $(0.64\%$ $[95\%$ CI 0.01-2.23]) and only one
                      occurrence of a GvH-like reaction across 334 infused
                      patients enrolled in the included studies, highlighting the
                      remarkable safety profile of CAR-engineered 'off-the-shelf'
                      allogeneic approaches. The estimated overall incidence of
                      low-grade CRS was $30\%$ $[95\%$ CI, 14-48], while the
                      estimated overall incidence of low-grade ICANS was $1\%$
                      $[95\%$ CI, $0\%-4\%],$ markedly lower than
                      current-generation autologous CAR-T cell products. The
                      incidence of low-grade and severe infections was $25\%$
                      $[95\%$ CI $14-36\%)$ (n=252) and $7\%$ $[95\%$ CI $2-14\%]$
                      (n=291), respectively.Together, allogeneic CAR-T and CAR-NK
                      cell therapies demonstrate encouraging efficacy in heavily
                      pretreated patients with r/r LBCL. Coupled with their
                      favorable safety profiles and the potential for
                      off-the-shelf availability, allogeneic cell therapies hold
                      great promise to broaden the reach of live cell-based
                      treatments, delivering impactful results to a wider patient
                      population in the coming years.},
      subtyp        = {Review Article},
      keywords     = {Humans / Immunotherapy, Adoptive: methods / Immunotherapy,
                      Adoptive: adverse effects / Receptors, Chimeric Antigen:
                      immunology / Receptors, Chimeric Antigen: genetics /
                      Lymphoma, Large B-Cell, Diffuse: therapy / Lymphoma, Large
                      B-Cell, Diffuse: immunology / Treatment Outcome / Neoplasm
                      Recurrence, Local: therapy / Killer Cells, Natural:
                      immunology / Killer Cells, Natural: transplantation /
                      Transplantation, Homologous / CRISPR gene editing (Other) /
                      adoptive cell therapy (ACT) (Other) / allogeneic CAR-NK
                      cells (Other) / allogeneic CAR-T cells (Other) / cellular
                      engineering (Other) / clinical trial (Other) / large B cell
                      lymphoma (Other) / precision gene editing (Other) /
                      Receptors, Chimeric Antigen (NLM Chemicals)},
      cin          = {MU01},
      ddc          = {610},
      cid          = {I:(DE-He78)MU01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40698082},
      pmc          = {pmc:PMC12279871},
      doi          = {10.3389/fimmu.2025.1585556},
      url          = {https://inrepo02.dkfz.de/record/303085},
}