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

German Dermatologic Cooperative Oncology Group (DeCOG Committee Ocular Melanoma)

doi:10.3390/cancers13133359

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

German Dermatologic Cooperative Oncology Group (DeCOG Committee Ocular Melanoma)

Clinic of Dermatology, Allergology and Venerology

28 Citations (Scopus)

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, 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.

Original language	English
Article number	3359
Journal	Cancers
Volume	13
Issue number	13
ISSN	2072-6694
DOIs	https://doi.org/10.3390/cancers13133359
Publication status	Published - 01.07.2021

Funding

M.V.H. was supported by the clinician scientist program awarded by the German Society of Dermatology (DDG) and the Arbeitsgemeinschaft Dermatologische Forschung (ADF). Acknowledgments: We thank all investigators of the German Dermatologic Cooperative Oncology Group (DeCOG) for their general commitment to the research consortium, in particular for the Committee Ocular Melanoma and participation in the ADOReg registry. Conflicts of Interest: F.M. has received travel support or/and speaker’s fees or/and advisor’s honoraria from Novartis, Roche, BMS, MSD and Pierre Fabre and research funding from Novartis and Roche. C.P. received honoraria (speaker honoraria or honoraria as a consultant) and travel support from: Novartis, BMS, Roche, Merck Serono, MSD, Celgene, AbbVie, SUNPHARMA, UCB, Allergy Therapeutics and LEO. S.U. declares research support from Bristol Myers Squibb and Merck Serono; speakers and advisory board honoraria from Bristol Myers Squibb, Merck Sharp & Dohme, Merck Serono, Novartis and Roche, and travel support from Bristol Myers Squibb, and Merck Sharp & Dohme. J.C.H. declares research support from BMS, advisory board honoraria from Pierre Fabre, Sanofi, Sunpharma and MSD, speakers honoraria from BMS, MSD, Novartis, Roche, Sanofi and Almirall and travel support from Pierre Fabre. F.Z. declares speakers and advisory board honoraria and/or travel support from BMS, MSD, Roche, Novartis, Pierre-Fabre and Sanofi-Aventis outside the submitted work. RG Research support: Pfizer, Johnson&Johnson, Novartis, Amgen, MerckSerono, SUN Pharma, Sanofi. Honoraria for lectures: Roche Pharma, Bristol-MyersSquibb, Novartis, MSD, Almirall-Hermal, Amgen, Merck-Serono, SUN, Pierre-Fabre, Sanofi, SUN Pharma, Bayer Honoraria for advisory boards: Roche Pharma, Bristol-MyersSquibb, Novartis, MSD, Almirall-Hermal, Amgen, Pierre-Fabre, Merck-Serono, 4SC, Immunocore, SUN Pharma, Sanofi, Pfizer. P.T.: BMS, Novartis, MSD, Pierre-Fabre, CureVac, Roche, Kyowa Kirin, Biofrontera, Invited Speaker, Personal BMS, Novartis, Pierre-Fabre, Merck Serono, Sanofi, Roche, Kyowa Kirin, Advisory Board, Personal BMS, Pierre-Fabre, Other, Personal, Travel support. B.S.T. declares advisory board honoraria from Iovance. M.S. reports receiving honoraria and participation in advisory boards of Bristol-Myers Squibb, Novartis, MSD, Roche, Pierre Fabre, Kyowa Kirin, Immunocore and Sanofi-Genzyme. M.S. received travel accommodation and expenses by Novartis, Pierre Fabre, and Sun Pharma. AG speaker’s honoraria from Bristol-Myers Squibb, MSD Sharp & Dohme and Roche; intermittent advisory board relationships with Amgen, Bristol-Myers Squibb, Novartis, MSD Sharp & Dohme, Pierre Fabre Pharmaceuticals, Pfizer, Roche and Sanofi Genzyme; travel and congress fee support from Bristol-Myers Squibb, MSD Sharp & Dohme, Novartis, Pierre Fabre Pharmaceuticals and Roche. Clinical studies: Amgen, Array, Bristol-Myers Squibb, GSK, Novartis, Merck, MSD Sharp & Dohme, Pfizer and Roche. K.M.T. received speaker or consultant honoraria and travel support from Bristol-Myers Squibb, Merck Sharp and Dohme, Roche, Novartis, Pierre Fabre, Sanofi Genzyme, LEO, Galderma, Almirall, La Roche-Posay and Candela. Funding: M.V.H. was supported by the clinician scientist program awarded by the German Society of Dermatology (DDG) and the Arbeitsgemeinschaft Dermatologische Forschung (ADF).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

DFG Research Classification Scheme

2.21-05 Immunology
2.22-14 Hematology, Oncology
2.22-19 Dermatology

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10.3390/cancers13133359

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@article{de1ed69ddb114032993a2c75c39b3c40,

title = "Immune checkpoint blockade for metastatic uveal melanoma: Patterns of response and survival according to the presence of hepatic and extrahepatic metastasis",

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, 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.",

author = "\{German Dermatologic Cooperative Oncology Group (DeCOG Committee Ocular Melanoma)\} and Koch, \{Elias A.T.\} and Anne Petzold and Anja Wessely and Edgar Dippel and Anja Gesierich and Ralf Gutzmer and Hassel, \{Jessica C.\} and Sebastian Haferkamp and Bettina Hohberger and K{\"a}hler, \{Katharina C.\} and Harald Knorr and Nicole Kreuzberg and Ulrike Leiter and Carmen Loquai and Friedegund Meier and Markus Meissner and Peter Mohr and Claudia Pf{\"o}hler and Farnaz Rahimi and Dirk Schadendorf and Beatrice Schell and Max Schlaak and Patrick Terheyden and Thoms, \{Kai Martin\} and Beatrice Schuler-Thurner and Selma Ugurel and Jens Ulrich and Jochen Utikal and Michael Weichenthal and Fabian Ziller and Carola Berking and Heppt, \{Markus V.\}",

note = "Publisher Copyright: Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

month = jul,

day = "1",

doi = "10.3390/cancers13133359",

language = "English",

volume = "13",

journal = "Cancers",

issn = "2072-6694",

number = "13",

}

Immune checkpoint blockade for metastatic uveal melanoma: Patterns of response and survival according to the presence of hepatic and extrahepatic metastasis. / German Dermatologic Cooperative Oncology Group (DeCOG Committee Ocular Melanoma).
In: Cancers, Vol. 13, No. 13, 3359, 01.07.2021.

Research output: Journal Articles › Journal articles › Research › peer-review

TY - JOUR

T1 - Immune checkpoint blockade for metastatic uveal melanoma

T2 - Patterns of response and survival according to the presence of hepatic and extrahepatic metastasis

AU - German Dermatologic Cooperative Oncology Group (DeCOG Committee Ocular Melanoma)

AU - Koch, Elias A.T.

AU - Petzold, Anne

AU - Wessely, Anja

AU - Dippel, Edgar

AU - Gesierich, Anja

AU - Gutzmer, Ralf

AU - Hassel, Jessica C.

AU - Haferkamp, Sebastian

AU - Hohberger, Bettina

AU - Kähler, Katharina C.

AU - Knorr, Harald

AU - Kreuzberg, Nicole

AU - Leiter, Ulrike

AU - Loquai, Carmen

AU - Meier, Friedegund

AU - Meissner, Markus

AU - Mohr, Peter

AU - Pföhler, Claudia

AU - Rahimi, Farnaz

AU - Schadendorf, Dirk

AU - Schell, Beatrice

AU - Schlaak, Max

AU - Terheyden, Patrick

AU - Thoms, Kai Martin

AU - Schuler-Thurner, Beatrice

AU - Ugurel, Selma

AU - Ulrich, Jens

AU - Utikal, Jochen

AU - Weichenthal, Michael

AU - Ziller, Fabian

AU - Berking, Carola

AU - Heppt, Markus V.

PY - 2021/7/1

Y1 - 2021/7/1

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, 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85111786780

U2 - 10.3390/cancers13133359

DO - 10.3390/cancers13133359

M3 - Journal articles

AN - SCOPUS:85111786780

SN - 2072-6694

VL - 13

JO - Cancers

JF - Cancers

IS - 13

M1 - 3359

ER -

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

Abstract

Funding

UN SDGs

DFG Research Classification Scheme

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