Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Heppt, Markus, V UNSPECIFIED UNSPECIFIED UNSPECIFIED Amaral, Teresa UNSPECIFIED UNSPECIFIED UNSPECIFIED Kaehler, Katharina C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Heinzerling, Lucie UNSPECIFIED UNSPECIFIED UNSPECIFIED Hassel, Jessica C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Meissner, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Kreuzberg, Nicole UNSPECIFIED UNSPECIFIED UNSPECIFIED Loquai, Carmen UNSPECIFIED UNSPECIFIED UNSPECIFIED Reinhardt, Lydia UNSPECIFIED UNSPECIFIED UNSPECIFIED Utikal, Jochen UNSPECIFIED UNSPECIFIED UNSPECIFIED Dabrowski, Evelyn UNSPECIFIED UNSPECIFIED UNSPECIFIED Gesierich, Anja UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfoehler, Claudia UNSPECIFIED UNSPECIFIED UNSPECIFIED Terheyden, Patrick UNSPECIFIED UNSPECIFIED UNSPECIFIED Thoms, Kai-Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Zimmer, Lisa UNSPECIFIED UNSPECIFIED UNSPECIFIED Eigentler, Thomas K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kirchberger, Michael C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Stege, Henner M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Meier, Friedegund UNSPECIFIED UNSPECIFIED UNSPECIFIED Schlaak, Max UNSPECIFIED UNSPECIFIED UNSPECIFIED Berking, Carola UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language MANAGEMENT; IPILIMUMAB; OUTCOMES Multiple languages Oncology; Immunology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/12769