Liver-directed treatment is associated with improved survival and increased response to immune checkpoint blockade in metastatic uveal melanoma: results from a retrospective multicenter trial.

Elias A T Koch; Anne Petzold; Anja Wessely; Edgar Dippel; Markus Eckstein; Anja Gesierich; Ralf Gutzmer; Jessica C Hassel; Harald Knorr; Nicole Kreuzberg; Ulrike Leiter; Carmen Loquai; Friedegund Meier; Markus Meissner; Peter Mohr; Claudia Pföhler; Farnaz Rahimi; Dirk Schadendorf; Max Schlaak; Kai-martin Thoms; Selma Ugurel; Jochen Utikal; Michael Weichenthal; Beatrice Schuler-thurner; Carola Berking; Markus V Heppt

Return

Liver-directed treatment is associated with improved survival and increased response to immune checkpoint blockade in metastatic uveal melanoma: results from a retrospective multicenter trial.

Author: Elias A T KOCH ¹ ; Anne PETZOLD ¹ ; Anja WESSELY ¹ ; Edgar DIPPEL ² ; Markus ECKSTEIN ³ ; Anja GESIERICH ⁴ ; Ralf GUTZMER ⁵ ; Jessica C HASSEL ⁶ ; Harald KNORR ⁷ ; Nicole KREUZBERG ⁸ ; Ulrike LEITER ⁹ ; Carmen LOQUAI ¹⁰ ; Friedegund MEIER ¹¹ ; Markus MEISSNER ¹² ; Peter MOHR ¹³ ; Claudia PFÖHLER ¹⁴ ; Farnaz RAHIMI ¹⁵ ; Dirk SCHADENDORF ¹⁶ ; Max SCHLAAK ¹⁷ ; Kai-Martin THOMS ¹⁸ ; Selma UGUREL ¹⁶ ; Jochen UTIKAL ¹⁹ ; Michael WEICHENTHAL ²⁰ ; Beatrice SCHULER-THURNER ¹ ; Carola BERKING ¹ ; Markus V HEPPT ²¹
Author Information

1. Department of Dermatology, Uniklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054, Erlangen, Germany.
2. Department of Dermatology, Ludwigshafen Medical Center, 67059, Ludwigshafen, Germany.
3. Comprehensive Cancer Center Erlangen-European Metropolitan Area of Nürnberg (CCC ER-EMN), 91054, Erlangen, Germany.
4. Department of Dermatology, University Hospital Würzburg, 97080, Würzburg, Germany.
5. Skin Cancer Center Minden, Department of Dermatology, Mühlenkreiskliniken AöR, Ruhr University, Bochum Campus Minden, 32423, Minden, Germany.
6. Skin Cancer Center, Department of Dermatology and National Center for Tumor Diseases (NCT), University Hospital Heidelberg, 69120, Heidelberg, Germany.
7. Department of Ophthalmology, Uniklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054, Erlangen, Germany.
8. Department of Dermatology and Venereology, Skin Cancer Center at the Center of Integrated Oncology (CIO) Köln Bonn, University Hospital of Cologne, 50937, Cologne, Germany.
9. Department of Dermatology, Center for Dermatooncology, University Hospital Tübingen, 72056, Tübingen, Germany.
10. Department of Dermatology, University Medical Center Mainz, 55131, Mainz, Germany.
11. Skin Cancer Center at the University Cancer Center Dresden and National Center for Tumor Diseases & Department of Dermatology, University Hospital Carl Gustav Carus, 01307, Dresden, Germany.
12. Department of Dermatology, Venereology and Allergology, Goethe University, 60590, Frankfurt am Main, Germany.
13. Department of Dermatology, Elbeklinikum, 21614, Buxtehude, Germany.
14. Department of Dermatology, Saarland University Medical School, 66421, Homburg/Saar, Germany.
15. Department of Dermatology and Allergy, Munich University Hospital (LMU), 81377, Munich, Germany.
16. Department of Dermatology, University Hospital Essen, University Duisburg-Essen, and German Cancer Consortium (DKTK), partner site, Essen/Düsseldorf, Germany, 45147.
17. Department of Dermatology, Venerology and Allergology, Charité -Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117, Berlin, Germany.
18. Department of Dermatology, University Medical Center Goettingen, 37075, Goettingen, Germany.
19. Skin Cancer Unit, German Cancer Research Center (DKFZ) and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, and DKFZ Hector Cancer Institute at the University Medical Center Mannheim, Mannheim, Germany.
20. Department of Dermatology, University Hospital Schleswig-Holstein, Campus Kiel, 24105, Kiel, Germany.
21. Department of Dermatology, Uniklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054, Erlangen, Germany. markus.heppt@uk-erlangen.de.
Publication Type:Multicenter Study
Keywords: SIRT; anti-CTLA-4; anti-PD-1; immune checkpoint blockade; liver-directed therapy; uveal melanoma
MeSH: Humans; CTLA-4 Antigen; Immune Checkpoint Inhibitors/therapeutic use*; Liver; Prospective Studies; Skin Neoplasms
From: Frontiers of Medicine 2023;17(5):878-888
CountryChina
Language:English
Abstract: Metastases of uveal melanoma (UM) spread predominantly to the liver. Due to low response rates to systemic therapies, liver-directed therapies (LDT) are commonly used for tumor control. The impact of LDT on the response to systemic treatment is unknown. A total of 182 patients with metastatic UM treated with immune checkpoint blockade (ICB) were included in this analysis. Patients were recruited from prospective skin cancer centers and the German national skin cancer registry (ADOReg) of the German Dermatologic Cooperative Oncology Group (DeCOG). Two cohorts were compared: patients with LDT (cohort A, n = 78) versus those without LDT (cohort B, n = 104). Data were analyzed for response to treatment, progression-free survival (PFS), and overall survival (OS). The median OS was significantly longer in cohort A than in cohort B (20.1 vs. 13.8 months; P = 0.0016) and a trend towards improved PFS was observed for cohort A (3.0 vs. 2.5 months; P = 0.054). The objective response rate to any ICB (16.7% vs. 3.8%, P = 0.0073) and combined ICB (14.1% vs. 4.5%, P = 0.017) was more favorable in cohort A. Our data suggest that the combination of LDT with ICB may be associated with a survival benefit and higher treatment response to ICB in patients with metastatic UM.