The association between immune checkpoint or BRAF/MEK inhibitor therapy and uveitis in patients with advanced cutaneous melanoma

• Published in: European journal of cancer (1990) Vol. 144; pp. 215 - 223
• Main Authors: Dimitriou, Florentia, Urner-Bloch, Ursula, Eggenschwiler, Corinne, Mitsakakis, Nicholas, Mangana, Joanna, Dummer, Reinhard, Urner, Martin
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2021; Elsevier Science Ltd
• Subjects: Aged; Bayesian analysis; Blindness; Conditional probability; Epidemiology; Female; Follow-Up Studies; Humans; Immune checkpoint; Immune checkpoint inhibitor; Immune Checkpoint Inhibitors - adverse effects; Inhibitors; Kinase inhibitor; Male; MAP Kinase Kinase Kinases - antagonists & inhibitors; MEK inhibitors; Melanoma; Melanoma - drug therapy; Melanoma - pathology; Melanoma, Cutaneous Malignant; Metastases; Middle Aged; Molecular Targeted Therapy; Patients; Probability; Prognosis; Protein Kinase Inhibitors - adverse effects; Proto-Oncogene Proteins B-raf - antagonists & inhibitors; Skin Neoplasms - drug therapy; Skin Neoplasms - pathology; Survival; Targeted treatment; Uveitis; Uveitis - chemically induced; Uveitis - pathology; Targeted treatment; Immune checkpoint inhibitor; Kinase inhibitor; Uveitis; Melanoma
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2020.11.027

Treatment with immune checkpoint and BRAF/MEK inhibitors has significantly improved the survival of patients with advanced cutaneous melanoma and other metastatic malignancies. Therapy-related uveitis is a rare ocular adverse event, which may potentially lead to legal blindness. The epidemiology of treatment-related uveitis is currently insufficiently known. In this cohort study, we asked whether exposure to either immune checkpoint or BRAF/MEK inhibitors was associated with a higher risk of developing uveitis compared with the general population. Based on a Bayesian framework, we estimated the probability of developing uveitis with a right-censored, exponential survival model using data from the Zurich Melanoma Registry. The registry included all adult patients treated for advanced cutaneous melanoma between January 2008 and December 2018 at the University Hospital of Zurich, Switzerland. In total, 304 patients (64%) were treated with immune checkpoint and 186 patients (38%) with BRAF/MEK inhibitors. Median follow-up time was 74 days (interquartile range: 57–233 days). Eleven patients developed uveitis and 30 patients died. We estimated the probability of developing uveitis per year in the general population as 0.05% (95% credibility interval [CrI]: 0.02%–0.1%). Corresponding posterior probabilities of treatment-related uveitis were 3.48% (95% CrI: 0.93%–7.49%) and 5.04% (95% CrI: 2.07%–9.19%) for immune checkpoint or BRAF/MEK inhibitors (posterior probability for difference: 76%). Immune checkpoint and particularly BRAF/MEK inhibitor therapies are associated with an increase in the risk of developing uveitis. Treatment-related uveitis is not associated with systemic adverse events of immune checkpoint or BRAF/MEK inhibitors. •Patients on immunotherapy or targeted therapies are at risk of developing uveitis.•Treatment-related uveitis is not associated with systemic adverse events.•The absence of symptoms does not rule out significant treatment-related uveitis.