Abstract
Simple SummaryImmune checkpoint inhibitors are increasingly being used for treating advanced malignant cutaneous melanoma and lung cancer. Immune-related side effects in multiple organs are common but the frequencies of ophthalmic side effects in national cohorts of unselected patients are undescribed. This study estimated frequencies of first-time ophthalmologist consultations and inflammatory conditions in consecutive patients with malignant melanoma or lung cancer treated with immune checkpoint inhibitors in Denmark from 2011–2018. The one-year risks of first-time consultation and ocular inflammation were 6% and 1%, respectively. These numbers were increased compared with patients with the same type of cancer who were not treated with immune checkpoint inhibitiors.Purpose: To estimate the frequency of first-time ocular events in patients treated with immune checkpoint inhibitors (ICI). Methods: Patients with cancer in 2011–2018 in Denmark were included and followed. The outcomes were first-time ophthalmologist consultation and ocular inflammation. One-year absolute risks of outcomes and hazard ratios were estimated. Results: 112,289 patients with cancer were included, and 2195 were treated with ICI. One year after the first ICI treatment, 6% of the patients with cancer, 5% and 8% of the lung cancer (LC) and malignant cutaneous melanoma (MM) patients, respectively, had a first-time ophthalmologist consultation. The risk of ocular inflammation was 1% (95% confidence interval (CI) 0.4–1.2). Among patients with MM, ICI was associated with ocular inflammation in women (HR 12.6 (95% CI 5.83–27.31) and men (4.87 (95% CI 1.79–13.29)). Comparing patients with and without ICI treatment, the risk of first-time ophthalmologist consultation was increased in patients with LC (HR 1.74 (95% CI 1.29–2.34) and MM (HR 3.21 (95% CI 2.31–4.44). Conclusions: The one-year risks of first-time ophthalmologist consultation and ocular inflammation were 6% and 1%, respectively, in patients treated with ICI. In patients with LC and MM, the risk was increased in patients with ICI compared with patients without ICI.
Highlights
Treatment with immune checkpoint inhibitors (ICI) may dramatically improve the survival in patients with malignant cutaneous melanoma, non-small cell lung cancer, Hodgkins’ lymphoma, urothelial carcinoma, squamous cell carcinoma, and renal cell carcinoma [1–4]
For each of the sub cohorts a cox model was used for analyzing each outcome
In patients with malignant cutaneous melanoma, ICI was associated with higher rates of both first-time ophthalmologist consultation at a secondary or tertiary hospital and ocular inflammation
Summary
Treatment with immune checkpoint inhibitors (ICI) may dramatically improve the survival in patients with malignant cutaneous melanoma, non-small cell lung cancer, Hodgkins’ lymphoma, urothelial carcinoma, squamous cell carcinoma, and renal cell carcinoma [1–4]. Of all patients with cancer in the USA, 1.54% in 2011 were estimated to be eligible for ICI treatment, and the number increased to 44% in 2018 [5]. PD1 is a surface receptor involved in regulating the exhaustion and tolerance of mainly T-cells Inhibiting these immune checkpoints with ICI therapy increases the immune system response primarily via CD8+T cells and counteracts the tumor cells immune system evasion [6–8]. We aimed to quantify the risk of first-time ophthalmologist consultation and ocular inflammation associated with ICI in a national cohort of Danish patients from 2011–2018. We found that ICI treatment with inhibitors of CTLA-4 (ipilimumab), PD1 (pembrolizumab and nivolumab), or PD-L1(atezolizumab and durvalumab) was associated with increased relative rates of both ocular inflammation and ophthalmologist consultations at secondary and tertiary hospitals
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