Screening for ocular toxicities of immunotherapy in a real-world population.

person Logan C. Barr School of Medicine, Queen's University, Kingston, ON, Canada info_outline Logan C. Barr, Jacob Rullo, Tara D. Baetz

Authors person Logan C. Barr School of Medicine, Queen's University, Kingston, ON, Canada info_outline Logan C. Barr, Jacob Rullo, Tara D. Baetz Organizations School of Medicine, Queen's University, Kingston, ON, Canada, Department of Ophthalmology, Queen's University, Kingston, ON, Canada, Division of Medical Oncology, Queen’s University, Kingston, ON, Canada Abstract Disclosures Research Funding No funding sources reported Background: Nivolumab, Pembrolizumab, and Ipilimumab have revolutionized the treatment of melanoma. However, patients receiving these treatments risk immunotherapy-related adverse events (IRAEs). IRAEs can occur in any organ system, are treated with steroids or immunosuppressive medications, and may require treatment delay or discontinuation. Ocular IRAEs, which are caused by off-target reactions with ocular immune mechanisms, are often identified after significant damage to the eye. Ocular IRAEs are rare in the literature with an approximate prevalence of 3.3%. After observing intraocular inflammation (uveitis) with uveal depigmentation (pigment release) in some patients receiving immunotherapy, we hypothesized that the rate of such events in a real-world population may be higher than previously reported. We predict ophthalmic screening and early intervention may prevent severe and potentially permanent ocular IRAEs. Methods: Patients starting immunotherapy for melanoma were referred to an ocular screening clinic at the Cancer Centre of Southeastern Ontario (Queen’s University, Kingston, Canada) for baseline ocular assessments. Repeat assessments occurred every three months (single agent) or at every cycle (dual immunotherapy). Intake visits included examination by an attending ophthalmologist, including examination for uveitis and anterior chamber free pigment under high-powered field. Intraocular inflammation (IOI) was defined as the presence of endothelial deposits and/or anterior chamber cell and/or pigment that was not present at baseline. Ocular findings were monitored alongside other IRAEs during treatment. Results: 28 patients (17 male, 11 female) receiving adjuvant (46.4%) or palliative (53.6%) immunotherapy for melanoma were evaluated. 9 of these patients received dual immunotherapy (Ipilimumab/Nivolumab) and 19 received single agent immunotherapy. IOI was identified in 11 patients (39.2%), while only 4 presented with symptoms. None of the patients had overt signs of anterior segment inflammation such as erythema, conjunctival injection, and chemosis. IOI developed in 54.5% of dual immunotherapy-treated patients. Patients with ocular IRAEs were treated with topical/systemic steroids or other immunosuppressive medications. None required discontinuation of immunotherapy. The development of IOI was more common in metastatic patients whose cancer was responding to immunotherapy, and many of these patients sustained IRAEs in other organ systems. Conclusions: Our findings suggest IOI related to ocular IRAEs are quite common and develop in a third of patients receiving immunotherapy for melanoma. Ocular screening for IOI identified early, often asymptomatic toxicities that could progress to permanent visual disability. Further evaluation of dedicated ocular screening is indicated in patients receiving immunotherapy.