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@ARTICLE{Ruf:289667,
      author       = {T. Ruf and R. Kramer and A. Forschner and U. Leiter and F.
                      Meier and L. Reinhardt and P. Dücker and C. Ertl and D.
                      Tomsitz and J. K. Tietze and R. Gutzmer and E. Dabrowski and
                      L. Zimmer$^*$ and A. Gesierich and S. Zierold and L. E.
                      French and T. Eigentler and T. Amaral and L. Heinzerling},
      title        = {{S}econd-line therapies for steroid-refractory
                      immune-related adverse events in patients treated with
                      immune checkpoint inhibitors.},
      journal      = {European journal of cancer},
      volume       = {203},
      issn         = {0014-2964},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2024-00849},
      pages        = {114028},
      year         = {2024},
      abstract     = {Immune checkpoint inhibitors (ICI) induce adverse events
                      (irAEs) that do not respond to steroids, i.e.
                      steroid-refractory (sr) irAEs, and irAEs in which steroids
                      cannot be tapered, i.e. steroid-dependent (sd) irAEs, in
                      about $10\%$ of cases. An evidence-based analysis of the
                      effectiveness of second-line immunosuppressive agents with
                      regard to irAE and tumor control is lacking.The
                      international web-based Side Effect Registry Immuno-Oncology
                      (SERIO; http://serio-registry.org) is a collaborative
                      initiative with the Paul-Ehrlich-Institute to document rare,
                      severe, complex or therapy-refractory immunotherapy-induced
                      side effects. The registry was queried on August 1, 2023 for
                      cases of irAEs which were treated with second-line
                      therapies.From a total of 1330 cases, 217 patients
                      $(16.3\%)$ received 249 second-line therapies. A total of 19
                      different second-line therapies were employed, including
                      TNF-alpha antagonists $(46.5\%),$ intravenous
                      immunoglobulins (IVIG; $19.1\%),$ mycophenolate mofetil
                      $(15.9\%),$ and methotrexate $(3.6\%).$ Therapy choices were
                      determined by the type of irAE. The time to onset of
                      sr-/sd-irAEs after ICI initiation did not consistently
                      differ from steroid-responsive irAEs. While $74.3\%$ of
                      sr-/sd-irAEs resolved and $13.1\%$ had improved, $4.3\%$
                      persisted, $3.9\%$ resulted in permanent sequelae, and
                      $4.3\%$ in death with ongoing symptoms. Infliximab exhibited
                      potential for earlier symptom improvement compared to
                      mycophenolate mofetil or IVIG. Tumor response in patients
                      with second-line treated sd-/sr-irAE was similar to patients
                      with irAEs treated with steroids only.Several second-line
                      therapies are effective against sr-/sd-irAEs, the
                      second-line therapies show no clear negative impact on tumor
                      response, and infliximab shows potential for faster
                      improvement of symptoms. However, prospective comparative
                      data are needed.},
      keywords     = {Immune checkpoint inhibitors (Other) / Immune-related
                      adverse events (Other) / Second-line immunosuppressants
                      (Other) / Steroid-dependent (Other) / Steroid-refractory
                      (Other)},
      cin          = {ED01},
      ddc          = {610},
      cid          = {I:(DE-He78)ED01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:38652976},
      doi          = {10.1016/j.ejca.2024.114028},
      url          = {https://inrepo02.dkfz.de/record/289667},
}