TY  - JOUR
A1  - Koch, Elias A. T.
A1  - Petzold, Anne
A1  - Wessely, Anja
A1  - Dippel, Edgar
A1  - Gesierich, Anja
A1  - Gutzmer, Ralf
A1  - Hassel, Jessica C.
A1  - Haferkamp, Sebastian
A1  - Hohberger, Bettina
A1  - Kähler, Katharina C.
A1  - Knorr, Harald
A1  - Kreuzberg, Nicole
A1  - Leiter, Ulrike
A1  - Loquai, Carmen
A1  - Meier, Friedegund
A1  - Meissner, Markus
A1  - Mohr, Peter
A1  - Pföhler, Claudia
A1  - Rahimi, Farnaz
A1  - Schadendorf, Dirk
A1  - Schell, Beatrice
A1  - Schlaak, Max
A1  - Terheyden, Patrick
A1  - Thoms, Kai-Martin
A1  - Schuler-Thurner, Beatrice
A1  - Ugurel, Selma
A1  - Ulrich, Jens
A1  - Utikal, Jochen
A1  - Weichenthal, Michael
A1  - Ziller, Fabian
A1  - Berking, Carola
A1  - Heppt, Markus
T1  - Immune checkpoint blockade for metastatic uveal melanoma: patterns of response and survival according to the presence of hepatic and extrahepatic metastasis
JF  - Cancers
N2  - 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.
KW  - uveal melanoma
KW  - immune checkpoint blockade
KW  - PD-1
KW  - CTLA-4
KW  - liver metastasis
KW  - treatment resistance
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-242603
SN  - 2072-6694
VL  - 13
IS  - 13
ER  - 
TY  - JOUR
A1  - Glutsch, Valerie
A1  - Kneitz, Hermann
A1  - Gesierich, Anja
A1  - Goebeler, Matthias
A1  - Haferkamp, Sebastian
A1  - Becker, Jürgen C.
A1  - Ugurel, Selma
A1  - Schilling, Bastian
T1  - Activity of ipilimumab plus nivolumab in avelumab-refractory Merkel cell carcinoma
JF  - Cancer Immunology, Immunotherapy
N2  - 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.
KW  - ipilimumab
KW  - Merkel cell carcinoma
KW  - resistance
KW  - avelumab
KW  - nivolumab
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265635
SN  - 14320851
VL  - 70
IS  - 7
ER  -