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Douglas B. Johnson and Jeffrey A. Sosman

is immune-based and includes ipilimumab and interleukin-2 (IL-2), which have activity regardless of BRAF mutational status. Ipilimumab is a monoclonal antibody that blocks the immune checkpoint CTLA-4 (cytotoxic T-lymphocyte antigen 4) and has

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Neelima N. Nallapaneni, Rajesh Mourya, Vijaya Raj Bhatt, Sakshi Malhotra, Apar Kishor Ganti, and Ketki K. Tendulkar

. Association of ipilimumab therapy for advanced melanoma with secondary adrenal insufficiency: a case series . Endocr Pract 2012 ; 18 : 351 – 355 . 14. Yang JC Hughes M Kammula U . Ipilimumab (anti-CTLA4 antibody) causes regression of metastatic

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Daniel G. Coit and Anthony J. Olszanski

However, interest has turned to new drug classes, including anti-CTLA4 antibodies and inhibitors of BRAF, which exploit the propensity of immune recognition and inhibition of signal-transduced growth/proliferation, respectively. The BRAF “driver” mutation

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Olumide Gbolahan, Neda Hashemi-Sadraei, and Bert O’Neil

response to CTLA-4 blockade in melanoma . N Engl J Med 2014 ; 371 : 2189 – 2199 . 25409260 10.1056/NEJMoa1406498 15. Rizvi H , Sanchez-Vega F , La K , . Molecular determinants of response to anti-programmed cell death (PD)-1 and anti

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Presenter: Smitha S. Krishnamurthi

have increased neoantigen loads that lead to CD8 infiltration; have high expression of immune checkpoints, including PD-1, PD-L1, CTLA-4, LAG-3, and IDO; and harbor more mutations compared with tumors that are MMR-proficient (ie, MSS). For treatment

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Lauren B. Banks and Sandra P. D’Angelo

tumors with a high TMB. Attempts to extend the use of ICI to STS are reviewed in this section. Anti–CTLA-4 and Anti–PD-1 Therapy SARC028, a multicenter, single-arm, phase II trial examining the efficacy of pembrolizumab in patients with either STS

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Kelly G. Paulson and Shailender Bhatia

: Ipilimumab (anti-CTLA4) has been used off-label in 5 patients with 2 successes. 54 Prospective trials of ipilimumab (either alone or in combination with radiation and/or nivolumab) are ongoing ( ClinicalTrials.gov identifiers: NCT03071406, NCT02488759) and

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Jarushka Naidoo

Another study showed that the microbiome is predictive not only of response but also of toxicity: the investigators demonstrated that the presence of a certain species of microbe may be protective against the development of colitis from anti–CTLA-4 therapy

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John A. Thompson

/unresectable melanoma. Ipilimumab is a human monoclonal antibody that binds to the cytotoxic T-lymphocyte antigen-4 (CTLA-4), blocks the corresponding immune checkpoint signal, and results in lymphocyte proliferation and immune stimulation. The FDA approved ipilimumab

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Douglas B. Johnson, Riyue Bao, Kristin K. Ancell, Anthony B. Daniels, Deborah Wallace, Jeffrey A. Sosman, and Jason J. Luke

-third of UMs will ultimately metastasize. 1 , 2 In the setting of metastatic disease, treatment options are limited and prognosis is poor. Immunotherapies, specifically those targeting PD-1 and cytotoxic T-lymphocyte antigen-4 (CTLA-4), have transformed