RESUMO
Balancing the potential for durable remissions with autoimmune-like toxicities is a key clinical challenge in the use of immune checkpoint inhibitors (ICI). Certain toxicities are associated with an increased response rate; however, the molecular underpinnings of this association are poorly understood. Here, we report a patient with wide spread uveal melanoma who had an exceptional response to treatment with ipilimumab and nivolumab, but suffered severe immune-related sequelae, including central serous retinopathy with retinal detachment, tinnitus, and vitiligo resembling Vogt-Koyanagi-Harada disease, and refractory enteritis. TCR-sequencing of the primary tumor, a hepatic metastasis, duodenal biopsy and peripheral blood mononuclear cells, identified the identical T cell clone in all four tissues. This case provides preliminary evidence for cross-reactivity as a mechanism for the association between effect and toxicity of ICIs.
Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Antígeno CTLA-4/antagonistas & inibidores , Ipilimumab/efeitos adversos , Melanoma/tratamento farmacológico , Nivolumabe/efeitos adversos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Doenças Retinianas/induzido quimicamente , Neoplasias Uveais/tratamento farmacológico , Síndrome Uveomeningoencefálica/induzido quimicamente , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/imunologia , Neoplasias Ósseas/secundário , Evolução Fatal , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/secundário , Melanoma/imunologia , Melanoma/patologia , Pessoa de Meia-Idade , Doenças Retinianas/imunologia , Linfócitos T/imunologia , Neoplasias Uveais/imunologia , Neoplasias Uveais/patologia , Síndrome Uveomeningoencefálica/imunologiaRESUMO
Although ipilimumab has been shown to improve survival in patients with metastatic melanoma and cause regression of metastatic renal cell carcinoma, the associated immune-related toxicities are of concern. The resultant T cell activation by this monoclonal antibody causes an increased immune response, which has been associated with many immune-regulated adverse effects. One of the most concerning effects is the development of colitis. Upwards to 8% of patients have been reported to develop colitis, with 5% being severe (Grades 3-4). While initial treatment of such adverse effects is generally comprised of supportive and symptomatic treatment, more severe cases warrant the use of high dose steroids. Furthermore, use of anti-TNF agents is usually reserved for those cases that prove to be refractory to steroids. We describe a systematic case review of seven patients who developed gastrointestinal symptoms following initiation of ipilimumab immunotherapy, and present the steps in their evaluation, treatment and outcomes at our institution.