Abstract
Purpose
To report a case of panuveitis and retinal vasculitis associated with pembrolizumab therapy for metastatic lung cancer.
Observations
A 71-year-old man, who was diagnosed with metastatic lung cancer (squamous cell carcinoma), presented with blurry vision 2 weeks after the initiation of pembrolizumab monotherapy. His best-corrected visual acuity (BCVA) was 20/20 OU, and slitlamp examination revealed fine keratic precipitates, anterior chamber cells (1+) and flare (1+) in both eyes. Dilated fundus examination showed no remarkable finding in the right eye and vitreous haze (2+), perivascular exudates, and vessel sheathing in the left eye. Fluorescence angiography demonstrated dye leakage from the optic disc and both retinal arteries and veins extending from the posterior to the peripheral retina in both eyes. The patient was diagnosed with panuveitis and retinal vasculitis as Grade 3 immune-related adverse event (irAE). Pembrolizumab was discontinued and oral prednisone 70mg/day was given for 1 week. The dose was reduced to 30mg/day for the next 3 weeks and was then stopped. One month after the treatment, intraocular inflammation became quiescent. With a good response to the treatment of irAE, pembrolizumab was restarted. Recurrence of ocular inflammation occurred over the next 1.5 years, but all of which were successfully treated with sub-Tenon’s injection of triamcinolone acetonide (STTA). The patient maintained BCVA of 30/20 OU at the latest visit.
Conclusions and importance
We showed a case of retinal vasculitis occurred as an irAE of pembrolizumab for metastatic lung cancer. Retinal vasculitis was well managed with transient pembrolizumab discontinuation and oral corticosteroid therapy, and pembrolizumab was restarted with the aid of STTA. As ocular irAEs might be controlled by local corticosteroid therapy, the decision to continue immune checkpoint inhibitor therapy should be made on a case-by-case basis.
1
Introduction
Since the first immune checkpoint inhibitor (ipilimumab) which targets cytotoxic T-lymphocyte antigen 4 (CTLA-4) was approved by the US Food and Drug Administration (FDA) in 2011 for treatment of metastatic melanoma, immune checkpoint inhibitor therapy has drastically changed the paradigm of cancer treatment. Currently approved immune checkpoint inhibitors by FDA target CTLA-4, programmed cell death 1 (PD-1) or its ligand, programmed cell death ligand 1 (PD-L1), and cancer immunotherapy using checkpoint inhibitors has considerably improved outcomes across many malignant tumors by activating immune reaction against cancer cells. However, as immune checkpoint proteins also suppress self-targeting immune response, immune checkpoint blockade can cause immune-related adverse events (irAEs).
The skin, gastrointestinal tract, and endocrine organs are frequently affected by immune checkpoint inhibitors, and the incidence rate of systemic irAEs was reported to be as high as 96% in the patients with advanced melanoma treated with nivolumab plus ipilimumab combination therapy. Although the reported frequency of ocular irAEs among patients treated with immune checkpoint inhibitors is not so high, some patients may experience a severe ocular irAE and lost their vision unless adequately treated. Herein, we present a rare case of panuveitis and retinal vasculitis associated with pembrolizumab (PD-1 inhibitor) therapy for metastatic lung cancer.
2
Case report
A 71-year-old man diagnosed as having right upper lobe squamous cell carcinoma (cT4N1M1b, StageⅣB) presented with blurry vision. He was started on pembrolizumab monotherapy 2 weeks prior, and skin rashes developed on his fingers and neck 9 days after pembrolizumab administration. He had a 46.5-pack-year history of smoking and had a medical history for chronic obstructive pulmonary disease. His ocular and family histories were unremarkable, and he had no known food and drug allergies. On initial examination, 18 days after the initiation of pembrolizumab, his best-corrected visual acuity (BCVA) was 20/20 OU. The intraocular pressure was 16 mmHg OD and 14 mmHg OS. Slitlamp examination revealed fine keratic precipitates, anterior chamber cells (1+) and flare (1+), and nuclear sclerotic cataract (2+) in both eyes. Dilated fundus examination showed no remarkable finding in the right eye and vitreous haze (2+), perivascular exudates, and vessel sheathing in the left eye. Optical coherence tomography (OCT) B-scan images of the macula appeared almost normal in the right eye and visualized multiple scattered hyperreflective spots in the neural retina in the left eye ( Fig. 1 ). Fluorescence angiography (FA) demonstrated dye leakage from the optic disc and both retinal arteries and veins extending from the posterior to the peripheral retina in both eyes. Indocyanine green angiography (ICGA) showed multifocal dye staining in retinal arteries on late-phase image ( Fig. 2 ). Systemic work-up to explore the cause of uveitis failed. Blood examinations showed elevated white blood cell count (10100/μL), ALP (344U/L), BUN (24.7 mg/dL), decreased albumin (3.9 g/dL), and negative for tuberculosis (negative T-SPOT), syphilis, toxoplasmosis, and fungal infection. Chest computed tomography neither showed bilateral hilar lymphadenopathy nor parenchymal lung changes.
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