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Immune checkpoint blockade for metastatic uveal melanoma: patterns of response and survival according to the presence of hepatic and extrahepatic metastasis

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 unc...

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Main Authors: Koch, Elias A. T. (Author) , Petzold, Anne (Author) , Wessely, Anja (Author) , Dippel, Edgar (Author) , Gesierich, Anja (Author) , Gutzmer, Ralf (Author) , Hassel, Jessica C. (Author) , Haferkamp, Sebastian (Author) , Hohberger, Bettina (Author) , Kähler, Katharina C. (Author) , Knorr, Harald (Author) , Kreuzberg, Nicole (Author) , Leiter-Stöppke, Ulrike (Author) , Loquai, Carmen (Author) , Meier, Friedegund (Author) , Meissner, Markus (Author) , Mohr, Peter (Author) , Pföhler, Claudia (Author) , Rahimi, Farnaz (Author) , Schadendorf, Dirk (Author) , Schell, Beatrice (Author) , Schlaak, Max (Author) , Terheyden, Patrick (Author) , Thoms, Kai-Martin (Author) , Schuler-Thurner, Beatrice (Author) , Ugurel, Selma (Author) , Ulrich, Jens (Author) , Utikal, Jochen (Author) , Weichenthal, Michael (Author) , Ziller, Fabian (Author) , Berking, Carola (Author) , Heppt, Markus V. (Author)
Format: Article (Journal)
Language:English
Published: 4 July 2021
In: Cancers
Year: 2021, Volume: 13, Issue: 13, Pages: 1-11
ISSN:2072-6694
DOI:10.3390/cancers13133359
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/cancers13133359
Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/2072-6694/13/13/3359
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Author Notes:Elias A.T. Koch, Anne Petzold, Anja Wessely, Edgar Dippel, Anja Gesierich, Ralf Gutzmer, Jessica C. Hassel, Sebastian Haferkamp, Bettina Hohberger, Katharina C. Kähler, Harald Knorr, Nicole Kreuzberg, Ulrike Leiter, Carmen Loquai, Friedegund Meier, Markus Meissner, Peter Mohr, Claudia Pföhler, Farnaz Rahimi, Dirk Schadendorf, Beatrice Schell, Max Schlaak, Patrick Terheyden, Kai-Martin Thoms, Beatrice Schuler-Thurner, Selma Ugurel, Jens Ulrich, Jochen Utikal, Michael Weichenthal, Fabian Ziller, Carola Berking, Markus V. Heppt and on behalf of the German Dermatologic Cooperative Oncology Group (DeCOG, Committee Ocular Melanoma)

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520 |a 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, χ2 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. 
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