Heppt, Markus, V, Amaral, Teresa, Kaehler, Katharina C., Heinzerling, Lucie, Hassel, Jessica C., Meissner, Markus, Kreuzberg, Nicole, Loquai, Carmen, Reinhardt, Lydia, Utikal, Jochen, Dabrowski, Evelyn, Gesierich, Anja, Pfoehler, Claudia, Terheyden, Patrick, Thoms, Kai-Martin, Zimmer, Lisa, Eigentler, Thomas K., Kirchberger, Michael C., Stege, Henner M., Meier, Friedegund, Schlaak, Max and Berking, Carola (2019). Combined immune checkpoint blockade for metastatic uveal melanoma: a retrospective, multi-center study. J. Immunother. Cancer, 7 (1). LONDON: BMC. ISSN 2051-1426

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Abstract

Background Uveal melanoma (UM) is highly refractory to treatment with dismal prognosis in advanced stages. The value of the combined checkpoint blockade with CTLA-4 and PD-1 inhibition in metastatic UM is currently unclear. Methods Patients with metastatic or unresectable UM treated with ipilimumab in combination with a PD-1 inhibitor were collected from 16 German skin cancer centers. Patient records of 64 cases were analyzed for response, progression-free survival (PFS), overall survival (OS), and safety. Clinical parameters and serum biomarkers associated with OS and treatment response were determined with Cox regression modelling and logistic regression. Results The best overall response rate to combined checkpoint blockade was 15.6% with 3.1 and 12.5% complete and partial response, respectively. The median duration of response was 25.5 months (range 9.0-65.0). Stable disease was achieved in 21.9%, resulting in a disease control rate of 37.5% with a median duration of the clinical benefit of 28.0 months (range 7.0-65.0). The median PFS was 3.0 months (95% CI 2.4-3.6). The median OS was estimated to 16.1 months (95% CI 12.9-19.3). Regarding safety, 39.1% of treated patients experienced a severe, treatment-related adverse event according to the CTCAE criteria (grade 3: 37.5%; grade 4: 1.6%). The most common toxicities were colitis (20.3%), hepatitis (20.3%), thyreoiditis (15.6%), and hypophysitis (7.8%). A poor ECOG performance status was an independent risk factor for decreased OS (p = 0.007). Conclusions The tolerability of the combined checkpoint blockade in UM may possibly be better than in trials on cutaneous melanoma. This study implies that combined checkpoint blockade represents the hitherto most effective treatment option available for metastatic UM available outside of clinical trials.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Heppt, Markus, VUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Amaral, TeresaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kaehler, Katharina C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heinzerling, LucieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hassel, Jessica C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meissner, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kreuzberg, NicoleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Loquai, CarmenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reinhardt, LydiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Utikal, JochenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dabrowski, EvelynUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gesierich, AnjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pfoehler, ClaudiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Terheyden, PatrickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thoms, Kai-MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zimmer, LisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eigentler, Thomas K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kirchberger, Michael C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stege, Henner M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meier, FriedegundUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schlaak, MaxUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Berking, CarolaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-127695
DOI: 10.1186/s40425-019-0800-0
Journal or Publication Title: J. Immunother. Cancer
Volume: 7
Number: 1
Date: 2019
Publisher: BMC
Place of Publication: LONDON
ISSN: 2051-1426
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MANAGEMENT; IPILIMUMAB; OUTCOMESMultiple languages
Oncology; ImmunologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/12769

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