New-onset uveitis during CTLA-4 blockade therapy with ipilimumab in metastatic melanoma patient

Miserocchi, Elisabetta; Cimminiello, Carolina; Mazzola, Marco; Russo, Vincenzo; Modorati, Giulio

doi:10.1016/j.jcjo.2014.10.010

Cited by 33 publications

(10 citation statements)

References 12 publications

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“…However, with the advent of newer agents, the awareness and development of adverse event management are crucial . Of note, immune‐mediated uveitis has also been reported with nivolumab, another PD‐1 inhibitor, and ipilimumab …”

Section: Discussionmentioning

confidence: 99%

A Rare Case of Pembrolizumab-Induced Uveitis in a Patient with Metastatic Melanoma

Hanna

2016

Pharmacotherapy

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Pembrolizumab, a programmed cell death protein 1 (PD-1) inhibitor, is a humanized monoclonal antibody used in the treatment of metastatic or unresectable melanoma and advanced non-small cell lung cancer (NSCLC). We hereby report a case of pembrolizumab-induced uveitis to increase practitioner awareness. A 78-year-old woman presented with onset of panuveitis after initiation of pembrolizumab therapy for metastatic melanoma. The patient received three cycles of therapy every 21 days, during which her symptoms progressively worsened. She was treated with topical and systemic corticosteroids, and further pembrolizumab was discontinued despite a good response to therapy. Pembrolizumab has been associated with rapid onset of ocular inflammation and uveitis. PD-1 inhibitors mediate a T-cell response against cancer cells; however, autoimmune complications have been reported. Incidence of pembrolizumab-induced uveitis is reported to be < 1%. To date, three cases have been reported since its Food and Drug Administration approval in September 2014. Uveitis, if left untreated, may lead to permanent vision loss and ocular damage. Cases of immune-mediated uveitis have been reported with cancer immunotherapies. Oncologists and ophthalmologists should be aware of this complication. With the increasing targeted pharmaceuticals in oncology, effective management of adverse events is necessary to ensure patient safety and optimal outcomes.

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Section: Discussionmentioning

confidence: 99%

A Rare Case of Pembrolizumab-Induced Uveitis in a Patient with Metastatic Melanoma

Hanna

2016

Pharmacotherapy

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“…However, targeting the immune system can trigger immune‐related adverse events (irAEs) involving various organ systems including gastrointestinal (enterocolitis, celiac disease, gastritis) , dermatologic (maculopapular rash, vitiligo, psoriasis) , and hepatic (hepatitis) , as well as endocrine. Less common immune toxicities can affect the nervous system (aseptic meningitis, Guillain‐Barré syndrome, peripheral neuropathy, encephalopathy) , lungs (pneumonitis, pleural effusion) , kidney (interstitial nephritis, glomerulonephritis) , pancreas (pancreatitis) , bone marrow (pancytopenia, neutropenia, thrombocytopenia, hemolytic anemia) , and eyes (uveitis, conjunctivitis, choroiditis, orbital myositis) . Early recognition and management of these toxicities is critical in reducing the occurrence of life‐threatening complications.…”

Section: Introductionmentioning

confidence: 99%

Endocrine-Related Adverse Events Related to Immune Checkpoint Inhibitors: Proposed Algorithms for Management

et al. 2019

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Immune checkpoint inhibitors have proven to be effective for various advanced neoplasia. Immune-related adverse events (irAEs) as a result of increased T cell activation are unique and potentially life-threating toxicities associated with the use of immune checkpoint inhibitors. Multiple endocrine irAEs, including primary hyperthyroidism and hypothyroidism, thyroiditis, primary adrenal insufficiency, type 1 diabetes mellitus, and hypophysitis, have been reported with the use of various immune checkpoint inhibitors. In some cases, these irAEs can lead to discontinuation of treatment. Here we propose for the general oncologist algorithms for managing endocrine irAEs to aid in the clinical care of patients receiving immunotherapy. The Oncologist 2020;25:290-300 KEY POINTS• There is a relative high risk of endocrine immune-related adverse events (irAEs) during therapy with checkpoint inhibitors, particularly when combination therapy is implemented. • Patients treated with anti-CTLA-4 antibodies have an increased risk of hypophysitis, whereas patients treated with anti-PD-1/PD-L1 antibodies have a higher risk of primary thyroid dysfunction. • Rarely, patients develop T1DM and central diabetes insipidus, and hypoparathyroidism is a rare occurrence. • A growing clinical understanding of endocrine irAEs has led to effective treatment strategies with hormone replacement.Correspondence: Jaydira

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“…BCR is a chronic, bilateral, and posterior uveitis that has an almost 100% genetic association with HLA-A29 [8]. Uveitis or uveitis masquerade syndrome could also be induced by some intraocular tumors, such as retinoblastoma and intraocular lymphoma, or their therapeutic approaches [9,10,11,12,13,14,15]. …”

Section: Introductionmentioning

confidence: 99%

Determination of Genes Related to Uveitis by Utilization of the Random Walk with Restart Algorithm on a Protein–Protein Interaction Network

Yan

et al. 2017

IJMS

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Uveitis, defined as inflammation of the uveal tract, may cause blindness in both young and middle-aged people. Approximately 10–15% of blindness in the West is caused by uveitis. Therefore, a comprehensive investigation to determine the disease pathogenesis is urgent, as it will thus be possible to design effective treatments. Identification of the disease genes that cause uveitis is an important requirement to achieve this goal. To begin to answer this question, in this study, a computational method was proposed to identify novel uveitis-related genes. This method was executed on a large protein–protein interaction network and employed a popular ranking algorithm, the Random Walk with Restart (RWR) algorithm. To improve the utility of the method, a permutation test and a procedure for selecting core genes were added, which helped to exclude false discoveries and select the most important candidate genes. The five-fold cross-validation was adopted to evaluate the method, yielding the average F1-measure of 0.189. In addition, we compared our method with a classic GBA-based method to further indicate its utility. Based on our method, 56 putative genes were chosen for further assessment. We have determined that several of these genes (e.g., CCL4, Jun, and MMP9) are likely to be important for the pathogenesis of uveitis.

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New-onset uveitis during CTLA-4 blockade therapy with ipilimumab in metastatic melanoma patient

Cited by 33 publications

References 12 publications

A Rare Case of Pembrolizumab-Induced Uveitis in a Patient with Metastatic Melanoma

A Rare Case of Pembrolizumab-Induced Uveitis in a Patient with Metastatic Melanoma

Endocrine-Related Adverse Events Related to Immune Checkpoint Inhibitors: Proposed Algorithms for Management

Determination of Genes Related to Uveitis by Utilization of the Random Walk with Restart Algorithm on a Protein–Protein Interaction Network

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