@article{KochPetzoldWesselyetal.2021,
  author    = {Koch, Elias A. T. and Petzold, Anne and Wessely, Anja and Dippel, Edgar and Gesierich, Anja and Gutzmer, Ralf and Hassel, Jessica C. and Haferkamp, Sebastian and Hohberger, Bettina and K{\"a}hler, Katharina C. and Knorr, Harald and Kreuzberg, Nicole and Leiter, Ulrike and Loquai, Carmen and Meier, Friedegund and Meissner, Markus and Mohr, Peter and Pf{\"o}hler, Claudia and Rahimi, Farnaz and Schadendorf, Dirk and Schell, Beatrice and Schlaak, Max and Terheyden, Patrick and Thoms, Kai-Martin and Schuler-Thurner, Beatrice and Ugurel, Selma and Ulrich, Jens and Utikal, Jochen and Weichenthal, Michael and Ziller, Fabian and Berking, Carola and Heppt, Markus},
  title     = {Immune checkpoint blockade for metastatic uveal melanoma: patterns of response and survival according to the presence of hepatic and extrahepatic metastasis},
  series = {Cancers},
  volume    = {13},
  journal   = {Cancers},
  number    = {13},
  issn      = {2072-6694},
  doi       = {10.3390/cancers13133359},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-242603},
  year      = {2021},
  abstract  = {Background: Since there is no standardized and effective treatment for advanced uveal melanoma (UM), the prognosis is dismal once metastases develop. Due to the availability of immune checkpoint blockade (ICB) in the real-world setting, the prognosis of metastatic UM has improved. However, it is unclear how the presence of hepatic and extrahepatic metastasis impacts the response and survival after ICB. Methods: A total of 178 patients with metastatic UM treated with ICB were included in this analysis. Patients were recruited from German skin cancer centers and the German national skin cancer registry (ADOReg). To investigate the impact of hepatic metastasis, two cohorts were compared: patients with liver metastasis only (cohort A, n = 55) versus those with both liver and extra-hepatic metastasis (cohort B, n = 123). Data were analyzed in both cohorts for response to treatment, progression-free survival (PFS), and overall survival (OS). The survival and progression probabilities were calculated with the Kaplan-Meier method. Log-rank tests, χ\(^2\) tests, and t-tests were performed to detect significant differences between both cohorts. Results: The median OS of the overall population was 16 months (95\% CI 13.4-23.7) and the median PFS, 2.8 months (95\% CI 2.5-3.0). The median OS was longer in cohort B than in cohort A (18.2 vs. 6.1 months; p = 0.071). The best objective response rate to dual ICB was 13.8\% and to anti-PD-1 monotherapy 8.9\% in the entire population. Patients with liver metastases only had a lower response to dual ICB, yet without significance (cohort A 8.7\% vs. cohort B 16.7\%; p = 0.45). Adverse events (AE) occurred in 41.6\%. Severe AE were observed in 26.3\% and evenly distributed between both cohorts. Conclusion: The survival of this large cohort of patients with advanced UM was more favorable than reported in previous benchmark studies. Patients with both hepatic and extrahepatic metastasis showed more favorable survival and higher response to dual ICB than those with hepatic metastasis only.},
  language  = {en}
}
@article{WeberGlutschGeissingeretal.2020,
  author    = {Weber, J. and Glutsch, V. and Geissinger, E. and Haug, L. and Lock, J.F. and Schneider, F. and Kneitz, H. and Goebeler, M. and Schilling, B. and Gesierich, A.},
  title     = {Neoadjuvant immunotherapy with combined ipilimumab and nivolumab in patients with melanoma with primary or in transit disease},
  series = {British Journal of Dermatology},
  volume    = {183},
  journal   = {British Journal of Dermatology},
  number    = {3},
  doi       = {10.1111/bjd.18739},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-213520},
  pages     = {559-563},
  year      = {2020},
  abstract  = {The introduction of new therapeutic agents has revolutionized the treatment of metastatic melanoma. The approval of adjuvant anti-programmed death-1 monotherapy with nivolumab or pembrolizumab, and dabrafenib plus trametinib has recently set a new landmark in the treatment of stage III melanoma. Now, clinical trials have shown that immune checkpoint blockade can be performed in a neoadjuvant setting, an approach established as a standard therapeutic approach for other tumour entities such as breast cancer. Recent studies suggest that a pathological response achieved by neoadjuvant immunotherapy is associated with long-term tumour control and that short neoadjuvant application of checkpoint inhibitors may be superior to adjuvant therapy. Most recently, neoadjuvant ipilimumab plus nivolumab in stage III melanoma was reported. With two courses of dose-optimized ipilimumab (1 mg kg-1) combined with nivolumab (3 mg kg-1), pathological responses were observed in 77\% of patients, while only 20\% of patients experienced grade 3 or 4 adverse events. However, the neoadjuvant trials employing combined immune checkpoint blockade conducted so far have excluded patients with in transit metastases, a common finding in stage III melanoma. Here we report four patients with in transit metastases or an advanced primary tumour who have been treated with neoadjuvant ipilimumab plus nivolumab according to the OpACIN-neo trial scheme (arm B). All patients achieved radiological disease control and a pathological response. None of the patients has relapsed so far.},
  language  = {en}
}
@article{KochPetzoldWesselyetal.2022,
  author    = {Koch, Elias A. T. and Petzold, Anne and Wessely, Anja and Dippel, Edgar and Gesierich, Anja and Gutzmer, Ralf and Hassel, Jessica C. and Haferkamp, Sebastian and K{\"a}hler, Katharina C. and Knorr, Harald and Kreuzberg, Nicole and Leiter, Ulrike and Loquai, Carmen and Meier, Friedegund and Meissner, Markus and Mohr, Peter and Pf{\"o}hler, Claudia and Rahimi, Farnaz and Schadendorf, Dirk and Schell, Beatrice and Schlaak, Max and Terheyden, Patrick and Thoms, Kai-Martin and Schuler-Thurner, Beatrice and Ugurel, Selma and Ulrich, Jens and Utikal, Jochen and Weichenthal, Michael and Ziller, Fabian and Berking, Carola and Heppt, Markus V.},
  title     = {Immune checkpoint blockade for metastatic uveal melanoma: re-induction following resistance or toxicity},
  series = {Cancers},
  volume    = {14},
  journal   = {Cancers},
  number    = {3},
  issn      = {2072-6694},
  doi       = {10.3390/cancers14030518},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-254814},
  year      = {2022},
  abstract  = {Re-induction with immune checkpoint blockade (ICB) needs to be considered in many patients with uveal melanoma (UM) due to limited systemic treatment options. Here, we provide hitherto the first analysis of ICB re-induction in UM. A total of 177 patients with metastatic UM treated with ICB were included from German skin cancer centers and the German national skin cancer registry (ADOReg). To investigate the impact of ICB re-induction, two cohorts were compared: patients who received at least one ICB re-induction (cohort A, n = 52) versus those who received only one treatment line of ICB (cohort B, n = 125). In cohort A, a transient benefit of overall survival (OS) was observed at 6 and 12 months after the treatment start of ICB. There was no significant difference in OS between both groups (p = 0.1) with a median OS of 16.2 months (cohort A, 95\% CI: 11.1-23.8) versus 9.4 months (cohort B, 95\% CI: 6.1-14.9). Patients receiving re-induction of ICB (cohort A) had similar response rates compared to those receiving ICB once. Re-induction of ICB may yield a clinical benefit for a small subgroup of patients even after resistance or development of toxicities.},
  language  = {en}
}