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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Douglas B. Johnson and Jeffrey A. Sosman
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
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
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
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
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
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
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
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
Presenter: Robin Kate Kelley
selection of ICIs (either as monotherapy or in combination) have received accelerated FDA approvals in the second-line setting based on earlier levels of data in phase I/II studies: nivolumab, 13 pembrolizumab, 14 and nivolumab in combination with the CTLA