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@ARTICLE{Jansen:299580,
      author       = {P. Jansen$^*$ and W. Galetzka and C. M. Thielmann$^*$ and
                      R. Murali and A. Zaremba$^*$ and F. Standl and G. Lodde$^*$
                      and I. Möller$^*$ and A. Sucker$^*$ and A. Paschen$^*$ and
                      E. Hadaschik$^*$ and S. Ugurel$^*$ and L. Zimmer$^*$ and E.
                      Livingstone$^*$ and D. Schadendorf$^*$ and A. Stang and K.
                      G. Griewank$^*$},
      title        = {p{TERT} mutational status is associated with survival in
                      stage {IV} melanoma patients receiving first-line immune
                      therapy.},
      journal      = {European journal of cancer},
      volume       = {220},
      issn         = {0959-8049},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2025-00521},
      pages        = {115337},
      year         = {2025},
      abstract     = {TERT promoter mutations are the most prevalent mutations in
                      melanoma. In this study, we investigated clinical
                      characteristics and survival after first line therapies in a
                      cohort of melanoma patients with known TERT promoter (pTERT)
                      mutation status.Sequencing data from 2013 to 2021 covering
                      29 genes and the pTERT status was assessed and 774 melanomas
                      patients with known pTERT status and clinical data were
                      analyzed. Progression free survival (PFS) and overall
                      survival (OS) of 374 melanoma patients in AJCC-stage IV who
                      received first-line immune checkpoint inhibitors (ICI,
                      anti-CTLA4 /anti-PD1 combination therapy or anti-PD1
                      monotherapy) or targeted therapy (TT) were assessed applying
                      Cox uni-/ multivariable analyses and Kaplan-Meier curves.The
                      cohort included 573 cutaneous, 69 mucosal, 37 acral and 95
                      MUP (melanomas of unknown primary) melanoma patients with a
                      median observational time from first diagnosis to patient
                      death or censoring of 38.5 months. TERT promoter mutations
                      were identified in 476 melanomas (61.5 $\%).$ Survival
                      analysis of 374 patients with stage IV disease undergoing
                      first-line systemic therapy (ICI or TT) suggested prolonged
                      PFS and OS for patients with pTERT mutation positive tumors
                      (pTERT(+)). Particularly, pTERT(+) patients receiving
                      anti-CTLA4/anti-PD1 therapy showed mPFS of 14.8 months (95
                      $\%$ CI: 7.1-40.3) and mOS of 105.2 months (95 $\%$ CI:
                      27.6-not reached) compared to pTERT(-) patients with mPFS of
                      5.5 months (95 $\%$ CI: 2.7-10.0) and mOS of 14.7 months (95
                      $\%$ CI: 11.7-24.1).Our findings suggest that presence of a
                      pTERT mutation in melanomas might favor PFS and OS after
                      first line ICI with the greatest improvement after receiving
                      anti-CTLA4 / anti-PD1. If validated in larger prospective
                      studies, pTERT mutation status may be a valuable prognostic
                      marker for stage IV melanoma patients.},
      keywords     = {Immune therapy (Other) / Melanoma (Other) / Mutational
                      profiling (Other) / PTERT (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:40056560},
      doi          = {10.1016/j.ejca.2025.115337},
      url          = {https://inrepo02.dkfz.de/record/299580},
}