@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{GlutschKneitzGesierichetal.2021, author = {Glutsch, Valerie and Kneitz, Hermann and Gesierich, Anja and Goebeler, Matthias and Haferkamp, Sebastian and Becker, J{\"u}rgen C. and Ugurel, Selma and Schilling, Bastian}, title = {Activity of ipilimumab plus nivolumab in avelumab-refractory Merkel cell carcinoma}, series = {Cancer Immunology, Immunotherapy}, volume = {70}, journal = {Cancer Immunology, Immunotherapy}, number = {7}, issn = {14320851}, doi = {10.1007/s00262-020-02832-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265635}, pages = {2087-2093}, year = {2021}, abstract = {Background Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine cutaneous malignancy with poor prognosis. In Europe, approved systemic therapies are limited to the PD-L1 inhibitor avelumab. For avelumab-refractory patients, efficient and safe treatment options are lacking. Methods At three different sites in Germany, clinical and molecular data of patients with metastatic MCC being refractory to the PD-L1 inhibitor avelumab and who were later on treated with combined IPI/NIVO were retrospectively collected and evaluated. Results Five patients treated at three different academic sites in Germany were enrolled. Three out of five patients investigated for this report responded to combined IPI/NIVO according to RECIST 1.1. Combined immunotherapy was well tolerated without any grade II or III immune-related adverse events. Two out of three responders to IPI/NIVO received platinum-based chemotherapy in between avelumab and combined immunotherapy. Conclusion In this small retrospective study, we observed a high response rate and durable responses to subsequent combined immunotherapy with IPI/NIVO in avelumab-refractory metastatic MCC patients. In conclusion, our data suggest a promising activity of second- or third-line PD-1- plus CTLA-4-blockade in patients with anti-PD-L1-refractory MCC.}, language = {en} }