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@ARTICLE{Gaughan:310361,
      author       = {E. M. Gaughan and M. Kim and I. Mendez and A. D. Rao and M.
                      Wei and A. So and X. Zhong and C. Berking and R. Jiang and
                      T. M. Kim and S. Dalle and C. Robert and S. Danson and S.
                      Alam and J. Charles and T. Davies and D. Debus and M.
                      Dzienis and R. Frazer and C. Gebhardt and G. Geidel and J.
                      Hassel$^*$ and I. Hansen and M. V. Heppt and L. Hildebrandt
                      and J. M. Isaacs and K. J. Suh and B. Keam and Y. J. Kim and
                      T. Lesimple and P. Saiag and A. Delibes and R. Barnett and
                      C. Krepler and K. Gandhi and N. Qizilbash and I. M. Shui and
                      X.-L. Tan and R. J. Sullivan},
      title        = {{R}esistance to anti-{PD}-1 immunotherapy for stage {III}
                      and {IV} melanoma: a global chart review study.},
      journal      = {Journal for ImmunoTherapy of Cancer},
      volume       = {14},
      number       = {3},
      issn         = {2051-1426},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {DKFZ-2026-00557},
      pages        = {e014564},
      year         = {2026},
      note         = {#NCTZFB9#},
      abstract     = {Anti-programmed cell death protein 1 (PD-1) immunotherapy
                      has revolutionized the treatment of stage III and IV
                      melanoma. Real-world data on its resistance is needed to
                      facilitate the development of combinatorial approaches to
                      overcome anti-PD-1 resistance.To characterize anti-PD-1
                      resistance and assess whether progressive disease assigned
                      by clinicians is concordant with scan data assessed by
                      independent central reviewers (ICR).A retrospective chart
                      review was conducted in adult patients with stage III/IV
                      melanoma who initiated anti-PD-1 therapy from January 2018
                      until 12 months before the start of data collection at 22
                      sites across six countries. Primary resistance and late
                      relapse in the adjuvant setting, and primary, secondary
                      resistance, and late progression in the advanced setting
                      were assigned using Society for Immunotherapy of Cancer
                      definitions. Demographic and clinical characteristics by
                      type of resistance were compared with appropriate univariate
                      tests. Time to resistance (TTR) and overall survival were
                      analyzed using Kaplan-Meier. To compare the concordance of
                      progression assigned by clinicians and ICR, the positive
                      predictive value (PPV) was calculated in a subset of
                      patients.Of 981 eligible patients, 738 were included. In the
                      adjuvant setting (n=240), 53 $(22.1\%)$ patients developed
                      primary resistance and 60 $(25.0\%)$ experienced late
                      relapse. In the advanced setting (n=498), 222 $(44.6\%),$ 50
                      $(10.0\%),$ and 64 $(12.9\%)$ patients developed primary,
                      secondary resistance, and late progression. Type of
                      resistance significantly differed by country, race, type of
                      BRAF mutation, and PD-L1 expression in both settings; and by
                      sex, disease stage and tumor thickness in the adjuvant
                      setting only (p<0.05). Mean (SD) TTR was 47.7 (1.3) and 24.2
                      (1.0) months in the adjuvant and advanced setting,
                      respectively. Patients with primary resistance had the
                      poorest overall survival. The PPV of progression assigned by
                      clinicians was $87.2\%$ $(95\%$ CI $72.6\%$ to
                      $95.7\%).This$ study showed that a substantial proportion of
                      patients with melanoma receiving anti-PD-1 therapy in the
                      adjuvant $(47.1\%)$ and advanced $(67.5\%)$ settings
                      developed resistance or late relapse/progression,
                      highlighting an unmet medical need. Real-world clinical
                      practice provided a reliable assessment of progression.
                      Factors associated with different types of resistance were
                      identified. Further study is warranted to evaluate their
                      impact on patient risk stratification. (Graphical
                      abstract).},
      keywords     = {Humans / Melanoma: drug therapy / Melanoma: pathology /
                      Melanoma: mortality / Melanoma: immunology / Male / Female /
                      Retrospective Studies / Middle Aged / Neoplasm Staging /
                      Drug Resistance, Neoplasm / Aged / Immune Checkpoint
                      Inhibitors: therapeutic use / Immune Checkpoint Inhibitors:
                      pharmacology / Adult / Immunotherapy: methods / Programmed
                      Cell Death 1 Receptor: antagonists $\&$ inhibitors / Skin
                      Neoplasms: drug therapy / Skin Neoplasms: pathology / Aged,
                      80 and over / Adjuvant (Other) / Immune Checkpoint Inhibitor
                      (Other) / Immunotherapy (Other) / Melanoma (Other) / Immune
                      Checkpoint Inhibitors (NLM Chemicals) / Programmed Cell
                      Death 1 Receptor (NLM Chemicals) / PDCD1 protein, human (NLM
                      Chemicals)},
      cin          = {HD02},
      ddc          = {610},
      cid          = {I:(DE-He78)HD02-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41786455},
      pmc          = {pmc:PMC12970133},
      doi          = {10.1136/jitc-2025-014564},
      url          = {https://inrepo02.dkfz.de/record/310361},
}