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@ARTICLE{Mallardo:284984,
      author       = {D. Mallardo and R. Woodford and A. M. Menzies and L.
                      Zimmer$^*$ and A. Williamson and E. Ramelyte and F.
                      Dimitriou and A. Wicky and R. Wallace and M. Mallardo and A.
                      Cortellini and A. Budillon and V. Atkinson and S. Sandhu and
                      M. Olivier and R. Dummer and P. Lorigan and D.
                      Schadendorf$^*$ and G. V. Long and E. Simeone and P. A.
                      Ascierto},
      title        = {{T}he role of diabetes in metastatic melanoma patients
                      treated with nivolumab plus relatlimab.},
      journal      = {Journal of translational medicine},
      volume       = {21},
      number       = {1},
      issn         = {1479-5876},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {DKFZ-2023-02168},
      pages        = {753},
      year         = {2023},
      abstract     = {The combination of nivolumab + relatlimab is superior to
                      nivolumab alone in the treatment of naive patients and has
                      activity in PD-1 refractory melanoma. We had previously
                      observed a reduced expression of LAG3 in melanoma tissue
                      from patients with type 2 diabetes.To evaluate the impact of
                      diabetes on oncological outcomes of patients with advanced
                      melanoma treated with nivolumab plus the LAG3 inhibitor
                      relatlimab we performed a retrospective multicenter
                      study.Overall, 129 patients were included: 88 without
                      diabetes before the treatment, 37 who were diagnosed with
                      type 2 diabetes before the start of treatment, and 4 without
                      diabetes before treatment who developed immune checkpoint
                      inhibitor-induced diabetes (ICI-DM). PFS was 21.71 months
                      $(95\%$ CI: 15.61-27.81) in patients without diabetes, 10.23
                      months $(95\%$ CI: 5.81-14.66) in patients with type 2
                      diabetes, and 50.85 months $(95\%$ CI: 23.04-78.65) in
                      patients who developed ICI-DM. OS was 37.94 months $(95\%$
                      CI: 31.02-44.85) in patients without diabetes, 22.12 months
                      $(95\%$ CI: 14.41-29.85) in those with type 2 diabetes and
                      57.64 months $(95\%$ CI: 42.29-72.99) in those who developed
                      ICI-DM. Multivariate analysis showed that the presence of
                      diabetes and LDH was correlated with OS and PFS. The mean OS
                      was 64.63 months in subjects with low levels of glucose (<
                      137 mg/dl) and 36.27 months in those with high levels
                      (hazard ratio 0.16, $95\%$ CI: 0.04-0.58; p = 0.005). The
                      patients whose glucose blood level increased after 3 months
                      of treatment with nivolumab + relatinib compared to baseline
                      (ratio of blood level at baseline/after 3 months > 1.5) had
                      a worse prognosis than those whose glucose level had not
                      increased. This result was observed also in subgroups
                      treated either in first line or further lines. Patients who
                      developed ICI-DM during the study period had better outcomes
                      than the overall population and patients without
                      diabetes.LAG3 inhibition for treating metastatic or
                      unresectable melanoma has a reduced efficacy in patients
                      with type 2 diabetes, possibly due to a low expression of
                      LAG3 in tumor tissue. Higher level evidence should be
                      obtained.},
      keywords     = {Diabetes (Other) / LDH (Other) / Melanoma (Other) /
                      Nivolumab + relatlimab (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:37880788},
      doi          = {10.1186/s12967-023-04607-4},
      url          = {https://inrepo02.dkfz.de/record/284984},
}