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

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BACKGROUND 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… Click to show full abstract

BACKGROUND 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. PATIENTS AND METHODS 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. RESULTS 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%). CONCLUSIONS 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.

Keywords: immune checkpoint; braf mek; checkpoint braf

Journal Title: European journal of cancer
Year Published: 2020

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