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@ARTICLE{Lipson:304299,
      author       = {E. J. Lipson and S. Dolfi and H. Tang and H. A. Tawbi and
                      F. Medina-Soto and E. Castillo Gutiérrez and P. Rutkowski
                      and H. Gogas and E. Murillo and P. A. Ascierto and K. Desai
                      and M. Maio and K. Demers and A. Mazzei and S. Keidel and K.
                      Miller-Moslin and J. X. Yu and F. S. Hodi and D.
                      Schadendorf$^*$ and G. V. Long and C. Garnett-Benson},
      title        = {{U}nraveling {R}elatlimab-{S}pecific {B}iology {U}sing
                      {B}iomarker {A}nalyses in {P}atients with {A}dvanced
                      {M}elanoma in {RELATIVITY}-047.},
      journal      = {Clinical cancer research},
      volume       = {31},
      number       = {17},
      issn         = {1078-0432},
      address      = {Philadelphia, Pa. [u.a.]},
      publisher    = {AACR},
      reportid     = {DKFZ-2025-01835},
      pages        = {3702 - 3714},
      year         = {2025},
      abstract     = {Administration of the lymphocyte activation gene 3 (LAG-3)
                      inhibitor relatlimab (RELA) and the PD-1 inhibitor nivolumab
                      (NIVO) significantly prolonged progression-free survival
                      (PFS) versus NIVO alone in patients with advanced melanoma
                      treated in RELATIVITY-047. This report describes correlative
                      analyses of biospecimens collected within that trial to
                      better understand the mechanisms of action and identify
                      patients who could benefit from treatment with NIVO +
                      RELA.Pre- and on-treatment peripheral blood samples from 563
                      patients were analyzed using flow cytometry for changes in
                      77 prespecified immune cell populations and using
                      immunoassay for peripheral IFNγ. Pretreatment tumor
                      biopsies were evaluated using IHC and RNA
                      sequencing.On-treatment expansion of 25 peripheral immune
                      cell populations was significantly greater with NIVO + RELA
                      versus NIVO alone. Responders to NIVO + RELA had greater
                      on-treatment increases in LAG-3+CD4+ T cells than
                      nonresponders. Significantly greater increases in peripheral
                      IFNγ occurred after treatment with NIVO + RELA versus NIVO
                      alone. A longer PFS was observed in patients treated with
                      NIVO + RELA whose tumors had low CD8 expression compared
                      with the NIVO arm. When evaluating the co-expression of CD8
                      and LAG-3, patients whose tumors had high CD8+LAG-3+ also
                      showed a PFS benefit with NIVO + RELA versus NIVO. RNA
                      sequencing revealed several distinct gene signatures
                      associated with response to NIVO + RELA.These results
                      highlight the unique biological effects of RELA in
                      combination with NIVO and provide further understanding of
                      the patient characteristics associated with increased
                      benefit from NIVO + RELA.},
      keywords     = {Humans / Melanoma: drug therapy / Melanoma: pathology /
                      Melanoma: genetics / Melanoma: mortality / Melanoma:
                      immunology / Biomarkers, Tumor: genetics / Female / Male /
                      Nivolumab: administration $\&$ dosage / Lymphocyte
                      Activation Gene 3 Protein / Middle Aged / Interferon-gamma /
                      Aged / Antigens, CD: genetics / Antigens, CD: metabolism /
                      Antibodies, Monoclonal, Humanized: administration $\&$
                      dosage / Programmed Cell Death 1 Receptor: antagonists $\&$
                      inhibitors / Antineoplastic Combined Chemotherapy Protocols:
                      therapeutic use / Adult / Immune Checkpoint Inhibitors:
                      administration $\&$ dosage / Progression-Free Survival /
                      Biomarkers, Tumor (NLM Chemicals) / Nivolumab (NLM
                      Chemicals) / Lymphocyte Activation Gene 3 Protein (NLM
                      Chemicals) / Interferon-gamma (NLM Chemicals) / Antigens, CD
                      (NLM Chemicals) / Antibodies, Monoclonal, Humanized (NLM
                      Chemicals) / Lag3 protein, human (NLM Chemicals) /
                      Programmed Cell Death 1 Receptor (NLM Chemicals) / Immune
                      Checkpoint Inhibitors (NLM Chemicals) / relatlimab (NLM
                      Chemicals)},
      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:40607902},
      pmc          = {pmc:PMC12402777},
      doi          = {10.1158/1078-0432.CCR-24-2499},
      url          = {https://inrepo02.dkfz.de/record/304299},
}