Bilateral Anterior Uveitis Associated with Nivolumab Therapy

Karlin, Justin; Gentzler, Ryan D.; Golen, Jeffrey

doi:10.1080/09273948.2016.1215473

Cited by 40 publications

(13 citation statements)

References 11 publications

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“…Uveitis was reported in 0.4% of patients during a phase III trial of pemrbolizumab, another anti-PD-1 monoclonal antibody [9]. Anterior uveitis emerged as an irAE in several case reports of patients receiving nivolumab and has responded to topical or intraocular steroids in each case [3–5]. …”

Section: Discussionmentioning

confidence: 99%

“…Nivolumab is approved by the Food and Drug Administration (FDA) for treatment of patients with non-surgical or metastatic melanoma, metastatic non-small cell lung cancer, renal cell carcinoma, classical Hodgkin’s lymphoma, squamous cell carcinoma of the head and neck, and urothelial carcinoma [2]. Published case reports have cited development of either secondary uveitis or ocular surface disease, separately, associated with use of the medication [3–6]. We present this as a case of bilateral and simultaneous keratitis and uveitis in the setting of nivolumab infusions for metastatic melanoma.…”

Section: Introductionmentioning

confidence: 99%

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Bilateral Uveitis and Keratitis Following Nivolumab Treatment for Metastatic Melanoma

Baughman¹,

Lee²,

Snydsman

et al. 2017

Med Case Rep

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Background Inflammatory eye disease has been reported as a side effect with Nivolumab. Case presentation We report a case of a 92-year-old woman presenting with bilateral and simultaneous keratitis and uveitis in the setting of recurring infusions of nivolumab for metastatic melanoma. The patient underwent successful coordinated treatment of both eyes coinciding with ongoing systemic infusion treatments with ophthalmic topical medications alone. Conclusion The interest of this case resides in the simultaneous nature of presentation of eye inflammation both internally and of the ocular surface. Prior case reports have cited uveitis or ocular surface disease, however not in simultaneous fashion. Clinicians should raise their index of suspicion of side effects of nivolumab systemic infusion for any vision or eye symptom changes around the timing of treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bilateral Uveitis and Keratitis Following Nivolumab Treatment for Metastatic Melanoma

Baughman¹,

Lee²,

Snydsman

et al. 2017

Med Case Rep

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“…These findings were assessed as uveitis (grade 3) related to his rhIL-15 treatment and possibly related to his prior treatment with high-dose IL-2 or ipilimumab or nivolumab, as was recently described (36) . The patient’s symptoms and uveitis resolved after treatment with high-dose corticosteroids.…”

Section: Safety and Toxicitymentioning

confidence: 99%

IL15 by Continuous Intravenous Infusion to Adult Patients with Solid Tumors in a Phase I Trial Induced Dramatic NK-Cell Subset Expansion

Conlon

Potter

Pittaluga

et al. 2019

Clinical Cancer Research

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Purpose: The first-in-human clinical trial with human bolus i.v. infusion IL-15 (rhIL-15) was limited by treatment-associated toxicity. Here, we report toxicity, immunomodulation, and clinical activity of rhIL-15 administered as a 10-day continuous intravenous infusion (CIV) to patients with cancers in a phase I trial. Patients and Methods: Patients received treatment for 10 days with CIV rhIL-15 in doses of 0.125, 0.25, 0.5, 1, 2, or 4 mcg/kg/day. Correlative laboratory tests included IL-15 pharmacokinetic (PK) analyses, and assessment of changes in lymphocyte subset numbers. Results: Twenty-seven patients were treated with rhIL-15; 2 mcg/kg/day was identified as the maximum tolerated dose (MTD). There were 8 serious adverse events including 2 bleeding events, papilledema, uveitis, pneumonitis, duodenal erosions and 2 deaths (one due to likely drug-related gastrointestinal ischemia). Evidence of antitumor effects were observed in several patients, but stable disease was the best response noted. Patients in 2 mcg/kg/day group had a 5.8-fold increase in number of circulating CD8+ T cells, 38-fold increase in total NK cells, and 358-fold increase in CD56bright NK cells. Serum IL-15 concentrations were markedly lower during the last 3 days of infusion. Conclusion: This phase I trial identified the MTD for CIV rhIL-15 and defined a treatment regimen that produced significant expansions of CD8+ T and NK effector cells in circulation and tumor deposits. This regimen has identified several biological features, including dramatic increases in numbers of NK cells, supporting trials of IL-15 with anticancer monoclonal antibodies to increase antibody-dependent cell-mediated cytotoxicity (ADCC) and anticancer efficacy.

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“…In one case reported by de Velasco and colleagues, nivolumab was associated with uveitis after cycle 28 (10 mg/kg, every 3 weeks) and in another case reported by Karlin and colleagues, the patient developed bilateral uveitis after cycle 10 (3 mg/kg, every 2 weeks) [ 4 , 5 ]. In contrast to these cases, the uveitis was not seen in our patient, however, we encountered bilateral optic neuritis after cycle 2 (3 mg/kg, every 2 weeks).…”

Section: Discussionmentioning

confidence: 99%

Bilateral Optic Neuritis Secondary to Nivolumab Therapy: A Case Report

Kartal

Ataş²

2018

Medicina

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Pediatric glioblastoma multiforme is an uncommon and highly mortal brain cancer. New therapeutic treatments are being intensively investigated by researchers in order to extend the survival of patients. The immune checkpoint inhibitor nivolumab in the treatment of pediatric glioblastoma multiforme is currently under review; it is a human immunoglobulin G4 monoclonal antibody that works against the programmed cell death protein 1 receptor, designed to enhance an immunologic reaction against cancer cells. Herein, we describe the first report of a bilateral optic neuritis induced by nivolumab in a grade 4 glioblastoma multiforme patient.

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Bilateral Anterior Uveitis Associated with Nivolumab Therapy

Cited by 40 publications

References 11 publications

Bilateral Uveitis and Keratitis Following Nivolumab Treatment for Metastatic Melanoma

Bilateral Uveitis and Keratitis Following Nivolumab Treatment for Metastatic Melanoma

IL15 by Continuous Intravenous Infusion to Adult Patients with Solid Tumors in a Phase I Trial Induced Dramatic NK-Cell Subset Expansion

Bilateral Optic Neuritis Secondary to Nivolumab Therapy: A Case Report

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