Uveitis in Patients Treated with CTLA-4 and PD-1 Checkpoint Blockade Inhibition

Sun, Michel M.; Levinson, Ralph D.; Filipowicz, Dorota; Anesi, Stephen D; Kaplan, Henry J.; Wang, Wei; Goldstein, Debra A.; Gangaputra, Sapna; Swan, Robert T.; Sen, H. Nida; Gordon, Lynn K.

doi:10.1080/09273948.2019.1577978

Cited by 58 publications

(47 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The onset of uveitis is reported mainly to occur within 2 months of starting CPIs. 7 , 13 , 26 This was generally the case in our cohort, with a median time to onset of 5 weeks (range 1–7 weeks). The exception was a single patient who developed anterior uveitis 2 years after completing 2 years of nivolumab treatment.…”

Section: Discussionsupporting

confidence: 65%

Ocular adverse events associated with immune checkpoint inhibitors: a novel multidisciplinary management algorithm

et al. 2021

View full text Add to dashboard Cite

Ocular immune-related adverse events (IrAEs) associated with use of checkpoint inhibitors (CPIs) in cancer therapeutics are relatively rare, occurring in approximately 1% of treated patients. Recognition and early intervention are essential because the degree of tissue damage may be disproportionate to the symptoms, and lack of appropriate treatment risks permanent loss of vision. International guidelines on managing ocular IrAEs provide limited advice only. Importantly, local interventions can be effective and may avoid the need for systemic corticosteroids, thereby permitting the continuation of CPIs. We present a single institution case series of eight affected patients managed by our multidisciplinary team. Consistent with previously published series and case reports, we identified anterior uveitis as the most common ocular IrAE associated with CPIs requiring intervention. Based on our experience, as well as published guidance, we generated a simple algorithm to assist clinicians efficiently manage patients developing ocular symptoms during treatment with CPIs. In addition, we make recommendations for optimising treatment of uveitis and address implications for ongoing CPI therapy.

show abstract

Section: Discussionsupporting

confidence: 65%

Ocular adverse events associated with immune checkpoint inhibitors: a novel multidisciplinary management algorithm

et al. 2021

View full text Add to dashboard Cite

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

“…In regards to the combination of ipilimumab and nivolumab, the ocular IRAEs described include dry eyes, corneal punctate epithelial erosions, subconjunctival hemorrhage, spontaneous corneal perforation, uveitis, hypotony maculopathy, cystoid macular edema, serous retinal detachment, choroiditis, VKH syndrome, optic neuritis, melanoma-associated retinopathy, and ocular myasthenia gravis [7, 8]. In 2 studies across 8 institutions, nearly all cases of ipilimumab-nivolumab associated uveitis were bilateral eye involvement and mild (trace cell) to moderate (1–2+ cell) in severity [7, 8].…”

Section: Discussionmentioning

confidence: 99%

Acute Bilateral Uveitis, Hypotony, and Cataracts Associated with Ipilimumab and Nivolumab Therapy: Optical Coherence Tomography Angiography Findings

Lee

Al-Humimat

Kooner

2020

Case Rep Ophthalmol

View full text Add to dashboard Cite

Immune checkpoint inhibitors are increasingly being used for the treatment of several malignancies. In rare cases, patients develop disabling ophthalmic side effects such as dry eyes, episcleritis, keratitis, uveitis, inflammatory orbitopathy, myasthenia gravis, macular edema, and serous retinal detachment. We present a case of acute bilateral anterior uveitis, prolonged hypotony, and cataracts following the use of dual therapy ipilimumab and nivolumab. Physicians should be aware of these immune-mediated ocular adverse events and should have a management plan to deal with these side effects that range from mild to vision threatening.

show abstract

Uveitis in Patients Treated with CTLA-4 and PD-1 Checkpoint Blockade Inhibition

Cited by 58 publications

References 54 publications

Ocular adverse events associated with immune checkpoint inhibitors: a novel multidisciplinary management algorithm

Ocular adverse events associated with immune checkpoint inhibitors: a novel multidisciplinary management algorithm

Autoimmune complications of immunotherapy: pathophysiology and management

Acute Bilateral Uveitis, Hypotony, and Cataracts Associated with Ipilimumab and Nivolumab Therapy: Optical Coherence Tomography Angiography Findings

Contact Info

Product

Resources

About