Exceptional response and multisystem autoimmune-like toxicities associated with the same T cell clone in a patient with uveal melanoma treated with immune checkpoint inhibitors. Issue 1 (4th March 2019)

• Record Type: Journal Article
• Authors: Rapisuwon, Suthee; Izar, Benjamin; Batenchuk, Cory; Avila, Alexandre; Mei, Shaolin; Sorger, Peter; Parks, Jerry M.; Cooper, Connor J.; Wagner, David; Zeck, Jay C.; Charabaty, Aline J.; Atkins, Michael B.
• Is Part Of: Journal for immunotherapy of cancer. Volume 7:Issue 1(2019)
• Publication Date: 2019-03-04
• Subjects: Cancer -- Immunotherapy -- Periodicals; Cancer -- Immunological aspects -- Periodicals; Tumors -- Immunological aspects -- Periodicals; Immunotherapy -- Periodicals; 616.99406105
• DOI: 10.1186/s40425-019-0533-0
• Languages: English
• ISSNs: 2051-1426

Abstract

Abstract : 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.