Severe pan-uveitis in a patient treated with vemurafenib for metastatic melanoma

Abstract

BackgroundVemurafenib, an inhibitor of genetically activated BRAF, is now commonly prescribed for metastatic melanoma harboring a BRAF mutation. Reports on side effects have focused on cutaneous complications. We here present a case of a severe pan-uveitis associated with vemurafenib use.Case presentationA 63-year old female was treated with the BRAF inhibitor vemurafenib for metastatic melanoma. After seven weeks of treatment, she developed near-complete visual loss in the course of a few days, as a result of severe uveitis. Vemurafenib had to be discontinued and systemic and topical corticosteroids were initiated. The visual symptoms improved slowly, however the cerebral metastases progressed and the patient died from her disease.ConclusionTreatment with vemurafenib has become an important component of standard clinical care for patients with metastatic melanoma. In addition, it is one of the best examples of genotype-directed therapy. This case illustrates that vemurafenib-induced uveitis can develop fast and be slow to resolve. Awareness of this potentially severe side effect is of major importance to oncologists and aggressive treatment should be considered.

Vogt‐Koyanagi‐Harada disease‐like posterior uveitis in the course of nivolumab (anti‐PD‐1 antibody), interposed by vemurafenib (BRAF inhibitor), for metastatic cutaneous malignant melanoma

“…A mean duration until the onset of uveitis after the start of vemurafenib was 5.6 months, with the range from 19 days to 7 months . Based on the previous experiences with vemurafenib , uveitis in the present patient, as an adverse event, had too earlier an onset after the administration. In addition, local administration of interferon could not be related with the onset of uveitis as the interferon injection was discontinued after lymph nodes metastases were found.…”

BRAF Inhibitors: Experience in Thyroid Cancer and General Review of Toxicity

“…One ocular AE associated with BRAF inhibitor use is uveitis, which has been reported to occur in 2% of vemurafenib-treated patients 76,121 and 1% of dabrafenib-treated patients 120,122 . Patients receiving these BRAF inhibitors should be monitored for symptoms of uveitis, which include blurred vision, photophobia, and ocular pain, and referred to an ophthalmologist if uveitis is suspected or if any vision changes occur.…”

Simultaneous Treatment of Severe Vemurafenib-induced Uveitis and Metastatic Melanoma

“…The relevant pathogenetic mechanisms are still not completely understood [8]. Both toxic and inflammatory reactions have been discussed [7,11,12]. Clinical observations suggest that there is a strong association between the intake of vemurafenib and the occurrence of ocular inflammation, which might be due to the response on subclinical metastatic cells within the uvea or to the erroneous interaction of vemurafenib with antigens shared by melanocytes and the choroid.…”

“…The anti-melanotic therapy was discontinued and steroids were applied systemically. The visual symptoms improved, but the patient died of progressive cerebral metastases [7]. Since the discontinuation of vemurafenib in such situations must be weighed carefully against the possibility of melanoma progression, it is crucial to devise alternative treatment approaches.…”

“…Topical or systemic treatment with steroids leads to recovery in many cases [2,6]. However, discontinuation of vemurafenib was recommended by some authors, especially in severe cases of uveitis [4,7], putting the patient at risk of melanoma progression [7]. In a review of clinical study reports from clinical pharmacology phase 1, 2, and 3 trials, Choe et al found that uveitis was the most common ocular adverse event in 568 patients treated with vemurafenib (4%).…”