TY  - JOUR
A1  - Heppt, Markus V.
A1  - Amaral, Teresa
A1  - Kähler, Katharina C.
A1  - Heinzerling, Lucie
A1  - Hassel, Jessica C.
A1  - Meissner, Markus
A1  - Kreuzberg, Nicole
A1  - Loquai, Carmen
A1  - Reinhardt, Lydia
A1  - Utikal, Jochen
A1  - Dabrowski, Evelyn
A1  - Gesierich, Anja
A1  - Pföhler, Claudia Ursula
A1  - Terheyden, Patrick
A1  - Thoms, Kai-Martin
A1  - Zimmer, Lisa
A1  - Eigentler, Thomas Kurt
A1  - Kirchberger, Michael Constantin
A1  - Stege, Henner Maximilian
A1  - Meier, Friedegund
A1  - Schlaak, Max
A1  - Berking, Carola
T1  - Combined immune checkpoint blockade for metastatic uveal melanoma: a retrospective, multi-center study
T2  - Journal for ImmunoTherapy of Cancer
N2  - 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.
KW  - Ipilimumab
KW  - Nivolumab
KW  - Combined immune checkpoint blockade
KW  - Uveal melanoma
KW  - Biomarker
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/53342
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-533420
SN  - 2051-1426
N1  - Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
VL  - 7
IS  - 1, Art. 299
SP  - 1
EP  - 9
PB  - BioMed Central
CY  - London
ER  -