Prevalence and Clinical Patterns of Ocular Complications Associated With Anti-PD-1/PD-L1 Anticancer Immunotherapy

Bitton, Karen; Michot, Jean‐Marie; Barreau, Emmanuel; Lambotte, Olivier; Haigh, Oscar; Marabelle, Aurélien; Voisin, Anne-Laure; Mateus, Christine; Rémond, A; Couret, C.; Champiat, Stéphane; Labétoulle, Marc; Rousseau, Antoine

doi:10.1016/j.ajo.2019.02.012

Cited by 69 publications

(55 citation statements)

References 42 publications

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“…A prospective case series that included 745 patients who were treated with anti–PD‐1/anti–PD‐L1 therapy described a total of 8 cases of ocular irAEs. Five of 8 patients with ocular irAEs had additional extraocular irAEs . Because ocular irAEs can be vision‐threatening, patients with new visual symptoms should be referred promptly to ophthalmology.…”

Section: Checkpoint Inhibitorsmentioning

confidence: 99%

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A review of cancer immunotherapy toxicity

Kennedy

Salama

2020

CA A Cancer J Clinicians

988

699

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Cancer immunotherapies, including checkpoint inhibitors and adoptive cell therapy, manipulate the immune system to recognize and attack cancer cells. These therapies have the potential to induce durable responses in multiple solid and hematologic malignancies and thus have transformed treatment algorithms for numerous tumor types. Cancer immunotherapies lead to unique toxicity profiles distinct from the toxicities of other cancer therapies, depending on their mechanism of action. These toxicities often require specific management, which can include steroids and immune‐modulating therapy and for which consensus guidelines have been published. This review will focus on the toxicities of checkpoint inhibitors and chimeric antigen receptor T cells, including pathophysiology, diagnosis, and management.

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Section: Checkpoint Inhibitorsmentioning

confidence: 99%

“…Five of 8 patients with ocular irAEs had additional extraocular irAEs. 93 Because ocular irAEs can be vision-threatening, patients with new visual symptoms should be referred promptly to ophthalmology. Grade 2 toxicity can be managed with topical corticosteroids, whereas grade 3 and 4 toxicities often require systemic corticosteroids.…”

Section: Ocular Toxicitymentioning

confidence: 99%

A review of cancer immunotherapy toxicity

Kennedy

Salama

2020

CA A Cancer J Clinicians

988

699

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“…Ocular ICI treatment can be complicated by uveitis, which can involve any segment 9697. Rare cases of Vogt-Koyanagi-Harada disease have also been described in patients with melanoma, suggesting that there may be cross reactivity between T cells targeting melanoma cells and healthy ocular melanocytes in these patients 98.…”

Section: Clinical Presentation Of Checkpoint Inhibitor Associated Autmentioning

confidence: 99%

Autoimmune complications of immunotherapy: pathophysiology and management

Chan

Bass

2020

BMJ

100

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Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that target inhibitory molecules, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), or its ligand, programmed cell death protein ligand 1 (PD-L1), and lead to immune activation in the tumor micro-environment. ICIs can induce durable treatment responses in patients with advanced cancers, but they are commonly associated with immune related adverse events (irAEs) such as rash, colitis, hepatitis, pneumonitis, and endocrine and musculoskeletal disorders. Almost all patients experience some form of irAE, but high grade irAEs occur in approximately half of those on combination therapy (eg, anti-CTLA-4 plus anti-PD-1), and up to one quarter receiving ICI monotherapy. Fatal irAEs occur in approximately 1.2% of patients on CTLA-4 blockade and 0.4% of patients receiving PD-1 or PD-L1 blockade, and case fatality rates are highest for myocarditis and myositis. IrAEs typically occur in the first three months after ICI initiation, but can occur as early as one day after the first dose to years after ICI initiation. The mainstay of treatment is with corticosteroids, but tumor necrosis factor inhibitors are commonly used for refractory irAEs. Although ICIs are generally discontinued when high grade irAEs occur, ICI discontinuation alone is rarely adequate to resolve irAEs. Consensus guidelines have been published to help guide management, but will likely be modified as our understanding of irAEs grows.

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“…Pooled analysis for OR (odds ratio) of all-grade immune-related ocular toxicities is 3.40 (95% CI: 1.32–8.71) ( 20 ). Due to the inherent characteristics of cohort studies, the prevalence of rare AEs such as ocular toxicities is somewhat underestimated, so the real incidence might be higher than expected ( 21 ). A disproportionality analysis of U.S. Food and Drug Administration (FDA) database FAERS demonstrated the reported odds ratios (RORs) of ICIs.…”

Section: Discussionmentioning

confidence: 99%