Concurrent Vogt–Koyanagi–Harada Disease and Impressive Response to Immune Checkpoint Blockade in Metastatic Melanoma

Gambichler, Thilo; Seifert, Caroline; Lehmann, Martin; Lukas, Carsten; Scheel, Christina; Susok, Laura

doi:10.2217/imt-2019-0206

Cited by 24 publications

(14 citation statements)

References 27 publications

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“…A very recent larger review of 126 cases of CPI-associated uveitis was broadly consistent, noting that 35% of panuveitis cases occurred as part of a Vogt-Koyanagi-Harada (VKH)-like syndrome. [27][28][29][30] VKH disease is a multisystem disease affecting melanin-containing tissues, which is thought to be autoimmune in origin. The most significant ocular manifestation is bilateral diffuse panuveitis with exudative retinal detachment, often accompanied by a variable spectrum of symptoms involving the skin, nervous system and inner ear.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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“…Genetic phenotype and viral infection are involved in the pathogenesis of the disease [7], and several cases of VKH disease-like uveitis after the initiation of ICI, which is often used in cancer treatment in recent years, have been reported. There are 15 cases of nivolumab-induced VKH disease-like uveitis, including ours [8][9][10][11][12][13][14][15][16][17][18][19][20] (Tables 1 and 2). Ophthalmic irAE are diverse, and the most common of which is uveitis (15.1%) [2].…”

Section: Discussionmentioning

confidence: 99%

Outcome of Nivolumab-Induced Vogt–Koyanagi–Harada Disease-Like Uveitis in a Patient Managed without Intravenous Methylprednisolone Therapy

Nagai

Yamamoto

Yoshida

et al. 2023

Case Reports in Ophthalmological Medicine

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Background. In recent years, immune checkpoint inhibitors (ICI) have been often used for several types of cancers. Immune-related adverse events (irAEs) are autoimmune responses caused by ICI. Among the different types of irAEs, uveitis is common in ophthalmology. Moreover, there are reports on Vogt–Koyanagi–Harada (VKH) disease-like uveitis. In most cases, VKH, as in the usual VKH, is managed with intravenous methylprednisolone therapy. Case Report. A 72-year-old man was diagnosed with gastric cancer, and he was treated with nivolumab, a type of ICI. After eight cycles of nivolumab therapy, he developed fulminant type 1 diabetes mellitus and diabetic ketoacidosis. Thus, the treatment was discontinued. Subsequently, the patient was referred to our department due to bilateral blurry vision. He had decreased visual acuity in both eyes, and slit lamp examination revealed the presence of bilateral anterior chamber cells and keratic precipitates. Fundus examination showed bilateral serous retinal detachment (SRD), wavy retinal pigment epithelium (RPE), and choroidal thickening. Cerebrospinal fluid examination revealed prominent pleocytosis. Thus, we initiated eye drop therapy and subtenon injection of triamcinolone acetonide on the right eye only. After 1 month, SRD and wavy RPE disappeared, and the patient’s visual acuity improved. Further, both eyes had similar improvements in visual acuity and abnormal findings. Oral prednisolone was subsequently administered for hearing loss. However, intravenous methylprednisolone was not used, and ophthalmologic findings and visual acuity did not change before and after systemic steroid therapy. One year after disease onset, SRD and wavy RPE did not relapse. Conclusion. Nivolumab-induced VKH disease-like uveitis can have good outcomes even in a patient managed without intravenous methylprednisolone therapy.

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“…Interestingly, evidence is accumulating that there may be a strong connection between autoimmune reactions, such as uveitis and vitiligo, and antimelanoma treatment response, both with MAPK inhibitors and ICI. 7,21,22 This is an important consideration as the discontinuation of these life-saving treatments could have important consequences in mortality rate. Although immune-related uveitis is rare, prompt management and screening are necessary to prevent vision loss and ocular damage.…”

Section: Discussionmentioning

confidence: 99%

“…2 Interestingly, VKH-like uveitis has been described in several case reports as a possible side effect of treatment with mitogen-activated protein kinase (MAPK) inhibitors (i.e., BRAF-and MEKinhibitors) and immune checkpoint inhibitors (ICI) in cancer patients. [3][4][5][6][7] We present a case of a patient with metastatic melanoma who developed a VKH-like uveitis during treatment with dabrafenib and trametinib, a BRAF and MEK inhibitor, four months after discontinuation of nivolumab, a PD-1 inhibitor. Two similar cases have already been reported by Fujimura et al 8 We provide in-depth insights into the possible (synergistic) role(s) of MAPK inhibitors and ICI in the development of this adverse effect.…”

mentioning

confidence: 99%

Vogt–koyanagi–harada Disease-Like Uveitis in a Patient With Advanced Melanoma Treated by Sequential Administration of Nivolumab and Dabrafenib/Trametinib Therapy

Madoe¹,

Schauwvlieghe²,

Jacob³

2023

RETINAL Cases &Amp; Brief Reports

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Purpose: To describe a case of bilateral Vogt-Koyanagi-Harada (VKH)-like uveitis during treatment with dabrafenib and trametinib and three months after discontinuation of nivolumab for malignant melanoma, and discuss the possible (synergistic) role(s) of mitogen-activated protein kinase (MAPK) inhibitors and immune checkpoint inhibitors in its pathophysiology.Methods: Retrospective case report with fluorescein angiography and optical coherence tomography.Results: A 55-year old patient with metastatic melanoma presented with a complaint of gradually worsening blurry vision in the right eye during treatment with dabrafenib and trametinib, three months after discontinuation of nivolumab. Based on the clinical examination, optical coherence tomography and fluorescein angiography findings, and a thorough laboratory work-up, he was diagnosed with a bilateral VKH-like uveitis without extraocular manifestations. The uveitis responded well to oral corticosteroids.Conclusion: Vogt-Koyanagi-Harada-like uveitis is a rare adverse effect of MAPK inhibitors and immune checkpoint inhibitors. Similar pathogenetic mechanisms including a drug-induced autoimmunity targeted against benign and malignant melanocytes may underlie MAPK inhibitor-induced and immune checkpoint inhibitors-induced VKH-like uveitis. In our report, the patient developed a VKH-like uveitis during MAPK inhibition therapy, four months after discontinuation of nivolumab. It is difficult to delineate whether MAPK inhibition alone was responsible for this adverse effect, or whether, on the contrary, potentiation occurred as a result of immune modulation by previous treatment with an immune checkpoint inhibitor. Further cases are needed to further clarify this latter hypothesis.

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Concurrent Vogt–Koyanagi–Harada Disease and Impressive Response to Immune Checkpoint Blockade in Metastatic Melanoma

Cited by 24 publications

References 27 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

Outcome of Nivolumab-Induced Vogt–Koyanagi–Harada Disease-Like Uveitis in a Patient Managed without Intravenous Methylprednisolone Therapy

Vogt–koyanagi–harada Disease-Like Uveitis in a Patient With Advanced Melanoma Treated by Sequential Administration of Nivolumab and Dabrafenib/Trametinib Therapy

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