Combined immune checkpoint blockade for metastatic uveal melanoma: A retrospective, multi-center study

Markus V. Heppt, Teresa Amaral, Katharina C. Kähler, Lucie Heinzerling, Jessica C. Hassel, Markus Meissner, Nicole Kreuzberg, Carmen Loquai, Lydia Reinhardt, Jochen Utikal, Evelyn Dabrowski, Anja Gesierich, Claudia Pföhler, Patrick Terheyden, Kai Martin Thoms, Lisa Zimmer, Thomas K. Eigentler, Michael C. Kirchberger, Henner M. Stege, Friedegund MeierMax Schlaak, Carola Berking*

*Corresponding author for this work
11 Citations (Scopus)


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.

Original languageEnglish
Article number299
JournalJournal for ImmunoTherapy of Cancer
Issue number1
Publication statusPublished - 13.11.2019

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)


Dive into the research topics of 'Combined immune checkpoint blockade for metastatic uveal melanoma: A retrospective, multi-center study'. Together they form a unique fingerprint.

Cite this