Ipilimumab Therapy in Patients With Advanced Melanoma and Preexisting Autoimmune Disorders

Johnson, Douglas B.; Sullivan, Ryan J.; Ott, Patrick A.; Carlino, Matteo S.; Khushalani, Nikhil I.; Ye, Fei; Guminski, Alexander; Puzanov, Igor; Lawrence, Donald P.; Buchbinder, Elizabeth I.; Mudigonda, Tejaswi; Spencer, Kristen; Bender, Carolin; Lee, Jenny; Kaufman, Howard L.; Menzies, Alexander M.; Hassel, Jessica C.; Mehnert, Janice M.; Sosman, Jeffrey A.; Long, Georgina V.; Clark, Joseph I.

doi:10.1001/jamaoncol.2015.4368

Cited by 563 publications

(458 citation statements)

References 30 publications

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“…Because of this, therapeutic use of check point inhibitors in patients with ADs developing tumors had mixed results so far. In a small cohort of AD patients that develop melanoma, CTLA4 blockade induces tumor growth inhibition, but 25-50% developed mild to moderate exacerbations of their AD or experienced conventional CTLA4-induced irAEs, respectively (10). Nevertheless, the high risk of IrAEs makes the use of checkpoint inhibitors controversial even in patients with certain autoimmune diseases (pernicious anemia, Crohn's disease, ulcerative colitis, SLE, and psoriasis) that develop tumors.…”

Section: Ifn-mediated Chronic Inflammation Checkpoint Inhibitors Anmentioning

confidence: 99%

Current prospects of type II interferon γ signaling and autoimmunity

Green

Young

Valencia

2017

Journal of Biological Chemistry

140

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Edited by Charles E. SamuelInterferon ␥ (IFN␥) is a pleiotropic protein secreted by immune cells. IFN␥ signals through the IFN␥ receptor, a protein complex that mediates downstream signaling events. Studies into IFN␥ signaling have provided insight into the general concepts of receptor signaling, receptor internalization, regulation of distinct signaling pathways, and transcriptional regulation. Although IFN␥ is the central mediator of the adaptive immune response to pathogens, it has been shown to be involved in several non-infectious physiological processes. This review will provide an introduction into IFN␥ signaling biology and the functional roles of IFN␥ in the autoimmune response.According to the National Institutes of Health, autoimmune diseases (ADs) 3 are one of the top 10 leading causes of death in female children and women in all age groups up to 64 years of age (1). Excess secretion of IFNs has been associated with development of human ADs (2). Interferons (IFNs) comprise a family of proteins classified as type I (IFN-␣, -␤, -⑀, -, and -), type II (IFN-␥, herein IFN␥), and type III (IFN-1-4) that have pleiotropic roles in immunity, cancer biology, and autoimmunity (2). Here, we aim to provide a basic understanding of the functions of the type II IFN␥ and the IFN␥-signaling pathway (hereafter referred to as IFN signaling) in a contextual and timing perspective related to the autoimmune environment and the development of ADs.

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Section: Ifn-mediated Chronic Inflammation Checkpoint Inhibitors Anmentioning

confidence: 99%

Current prospects of type II interferon γ signaling and autoimmunity

Green

Young

Valencia

2017

Journal of Biological Chemistry

140

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“…1 We report the case of a 50-year-old man who had metastatic colon cancer with a mismatchrepair deficiency and who had been treated with third-line pembrolizumab after disease progression while he was receiving FOLFOX (folinic acid, fluorouracil, and oxaliplatin) and FOLFIRI (folinic acid, fluorouracil, and irinotecan). The patient had mild psoriasis, for which he received topical treatment, and Crohn's disease, which had been treated with small-bowel resection and ileostomy in 2012.…”

Section: Reversal Of Autoimmune Toxicity and Loss Of Tumor Response Bmentioning

confidence: 99%

“…1 However, an understanding of potential biologic interference associated with this new technique is still evolving. Here, we present a case that A multiplex single-base primer extension assay (SNaPshot) was used as a complementary assay to evaluate hotspot mutation positions in IDH2 that were not covered by a next-generation sequencing panel.…”

Section: Correspondencementioning

confidence: 99%

Reversal of Autoimmune Toxicity and Loss of Tumor Response by Interleukin-17 Blockade

2017

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“…However, as the use of immunotherapy continues to expand into a broader, real-world population, patients with preexisting autoimmune disorders or immune-mediated adverse events (imAEs) from prior immunotherapy are being considered [107,108]. In one study, the use of the PD-1 blockers pembrolizumab or nivolumab in 119 patients with advanced melanoma and preexisting autoimmune disorders and/or imAEs from prior ipilimumab monotherapy resulted in an ORR of 37%, although approximately 10% of patients discontinued treatment because of imAEs [108].…”

Section: Immunotherapeutics and Patient Selectionmentioning

confidence: 99%

Immune Checkpoint Blockade: The New Frontier in Cancer Treatment

et al. 2018

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Immune checkpoint blockers have revolutionized cancer treatment in recent years. These agents are now approved for the treatment of several malignancies, including melanoma, squamous and non-squamous non-small cell lung cancer, renal cell carcinoma, urothelial carcinoma, and head and neck squamous cell carcinoma. Studies have demonstrated the significant impact of immunotherapy versus standard of care on patient outcomes, including durable response and extended survival. The use of immunotherapy-based combination therapy has been shown to further extend duration of response and survival. Immunotherapies function through modulation of the immune system, which can lead to immune-mediated adverse events (imAEs). These include a range of dermatologic, gastrointestinal, endocrine, and hepatic toxicities, as well as other less common inflammatory events. ImAEs are typically low grade and manageable when identified early and treated with appropriate measures. Identifying the right patient for the right therapy will become more important as new immunotherapies and immunotherapy-based combinations are approved and costs of cancer care continue to rise.

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Ipilimumab Therapy in Patients With Advanced Melanoma and Preexisting Autoimmune Disorders

Cited by 563 publications

References 30 publications

Current prospects of type II interferon γ signaling and autoimmunity

Current prospects of type II interferon γ signaling and autoimmunity

Reversal of Autoimmune Toxicity and Loss of Tumor Response by Interleukin-17 Blockade

Immune Checkpoint Blockade: The New Frontier in Cancer Treatment

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