Immune Checkpoint Blockade for Metastatic Uveal Melanoma: Re-Induction following Resistance or Toxicity

Elias A T Koch; Anne Petzold; Anja Wessely; Edgar Dippel; Anja Gesierich; Ralf Gutzmer; Jessica C Hassel; Sebastian Haferkamp; 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

doi:10.3390/cancers14030518

Immune Checkpoint Blockade for Metastatic Uveal Melanoma: Re-Induction following Resistance or Toxicity

Cancers (Basel). 2022 Jan 20;14(3):518. doi: 10.3390/cancers14030518.

Authors

Elias A T Koch^{1

2}, Anne Petzold^{1

2}, Anja Wessely^{1

2}, Edgar Dippel³, Anja Gesierich⁴, Ralf Gutzmer⁵, Jessica C Hassel⁶, Sebastian Haferkamp⁷, Katharina C Kähler⁸, Harald Knorr⁹, Nicole Kreuzberg¹⁰, Ulrike Leiter¹¹, Carmen Loquai¹², Friedegund Meier¹³, Markus Meissner¹⁴, Peter Mohr¹⁵, Claudia Pföhler¹⁶, Farnaz Rahimi¹⁷, Dirk Schadendorf^{18

19}, Beatrice Schell²⁰, Max Schlaak²¹, Patrick Terheyden²², Kai-Martin Thoms²³, Beatrice Schuler-Thurner^{1

2}, Selma Ugurel¹⁸, Jens Ulrich²⁴, Jochen Utikal²⁵, Michael Weichenthal⁸, Fabian Ziller²⁶, Carola Berking^{1

2}, Markus V Heppt^{1

2}

Affiliations

¹ Department of Dermatology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.
² Comprehensive Cancer Center Erlangen-European Metropolitan Area of Nuremberg (CCC ER-EMN), 91054 Erlangen, Germany.
³ Department of Dermatology, Ludwigshafen Medical Center, 67059 Ludwigshafen, 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 Dermatology, University Hospital Regensburg, 93053 Regensburg, Germany.
⁸ Department of Dermatology, University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.
⁹ Department of Ophthalmology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.
¹⁰ Department of Dermatology and Venereology, Skin Cancer Center, Center of Integrated Oncology (CIO) Köln Bonn, University Hospital of Cologne, 50937 Cologne, Germany.
¹¹ Department of Dermatology, Center for Dermatooncology, University Hospital Tübingen, 72056 Tübingen, Germany.
¹² Department of Dermatology, University Medical Center Mainz, 55131 Mainz, Germany.
¹³ Skin Cancer Center, University Cancer Center Dresden and National Center for Tumor Diseases & Department of Dermatology, University Hospital Carl Gustav Carus, 01307 Dresden, Germany.
¹⁴ Department of Dermatology, Venereology and Allergology, Goethe University, 60590 Frankfurt am Main, Germany.
¹⁵ Department of Dermatology, Elbeklinikum, 21614 Buxtehude, Germany.
¹⁶ Department of Dermatology, Saarland University Medical School, 66421 Homburg, Saar, Germany.
¹⁷ Department of Dermatology and Allergy, Munich University Hospital (LMU), 81377 Munich, Germany.
¹⁸ Department of Dermatology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany.
¹⁹ German Cancer Consortium, Partner Site Essen, 45147 Essen, Germany.
²⁰ Department of Dermatology, SRH Wald-Klinikum Gera, 07548 Gera, Germany.
²¹ Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Department of Dermatology, Venerology and Allergology, 10117 Berlin, Germany.
²² Department of Dermatology, University of Lübeck, 23562 Lübeck, Germany.
²³ Department of Dermatology, University Medical Center Goettingen, 37075 Goettingen, Germany.
²⁴ Department of Dermatology, Harzklinikum Dorothea Christiane Erxleben, 06484 Quedlinburg, Germany.
²⁵ Skin Cancer Unit, German Cancer Research Center (DKFZ) and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, 68167 Mannheim, Germany.
²⁶ Department of Dermatology, DRK Krankenhaus Rabenstein, 09117 Chemnitz, Germany.

Abstract

Re-induction with immune checkpoint blockade (ICB) needs to be considered in many patients with uveal melanoma (UM) due to limited systemic treatment options. Here, we provide hitherto the first analysis of ICB re-induction in UM. A total of 177 patients with metastatic UM treated with ICB were included from German skin cancer centers and the German national skin cancer registry (ADOReg). To investigate the impact of ICB re-induction, two cohorts were compared: patients who received at least one ICB re-induction (cohort A, n = 52) versus those who received only one treatment line of ICB (cohort B, n = 125). In cohort A, a transient benefit of overall survival (OS) was observed at 6 and 12 months after the treatment start of ICB. There was no significant difference in OS between both groups (p = 0.1) with a median OS of 16.2 months (cohort A, 95% CI: 11.1-23.8) versus 9.4 months (cohort B, 95% CI: 6.1-14.9). Patients receiving re-induction of ICB (cohort A) had similar response rates compared to those receiving ICB once. Re-induction of ICB may yield a clinical benefit for a small subgroup of patients even after resistance or development of toxicities.

Keywords: CTLA-4; PD-1; immune checkpoint blockade; re-induction; toxicity; treatment resistance; uveal melanoma.