inhibitor alone or in combination with a CTLA-4 inhibitor. In addition, 5 of the lymphoma studies evaluated gene-modified stem cell trials with or without cytotoxic chemotherapy, with 1 phase I/II allogeneic Epstein-Barr virus (EBV)–specific cytotoxic T
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Rachel A. Bender Ignacio, Lilie L. Lin, Lakshmi Rajdev, and Elizabeth Chiao
Chandan Kumar-Sinha and Vaibhav Sahai
anti–CTLA-4 antibody ipilimumab are approved as the second-line treatment of HCC after sorafenib, based on early- and late-phase trial results. 22 – 24 In contrast, a similar benefit has not been realized in BTCs, wherein only a small subset of
Katherine M. Bever and Dung T. Le
characterized by exceptionally high mutation burden and an immune-active tumor microenvironment with high levels of tumor-infiltrating lymphocytes (TILs) and high levels of expression of multiple immune checkpoints, including PD-1, PD-L1, CTLA-4, LAG3, and IDO
Eric H. Bent, Eric Wehrenberg-Klee, Eugene J. Koay, Lipika Goyal, and Jennifer Y. Wo
, with nivolumab in combination with the CTLA-4 inhibitor ipilimumab showing an ORR of 32% in the second-line setting, suggesting a promising route forward in treating this disease. 24 In May 2020, a combination of the PD-L1 inhibitor atezolizumab and
Stephanie Andrews
Nurse Practitioner, Moffitt Cancer Center. Autoimmunity is recognized as an effect of prolonged T-cell activation via inhibition of either CTLA-4 or the programmed death protein receptor (PD-1) and its ligand (PD-L1). “We need to balance the efficacy
Kelsey C. Stoltzfus, Biyi Shen, Leila Tchelebi, Daniel M. Trifiletti, Niraj J. Gusani, Vonn Walter, Ming Wang, and Nicholas G. Zaorsky
. Checkpoint inhibitor immunotherapy (with anti–PD-1, anti–PD-L1, or anti–CTLA-4 agents) was not available in the market until about 2014. Moreover, the percentage of patients estimated to respond to checkpoint inhibitor drugs was 0.14% in 2011 and increased to
Saranya Chumsri, Ethan S. Sokol, Aixa E. Soyano-Muller, Ricardo D. Parrondo, Gina A. Reynolds, Aziza Nassar, and E. Aubrey Thompson
to dMMR status, recent studies have shown that TMB itself is also predictive of improved outcome in patients receiving ICIs. Initial studies in melanoma have shown that high TMB was associated with improved outcomes in patients receiving anti–CTLA-4
Ravi A. Madan, Thomas Schwaab, and James L. Gulley
(YERVOY; Bristol-Myers Squibb, New York, NY) has shown delayed effects in metastatic melanoma. 15 This monoclonal antibody serves as an immune checkpoint inhibitor by blocking T-cell interactions with the CTLA-4 molecule on APCs after T-cell activation
Daniel G. Coit, John A. Thompson, Mark R. Albertini, Christopher Barker, William E. Carson III, Carlo Contreras, Gregory A. Daniels, Dominick DiMaio, Ryan C. Fields, Martin D. Fleming, Morganna Freeman, Anjela Galan, Brian Gastman, Valerie Guild, Douglas Johnson, Richard W. Joseph, Julie R. Lange, Sameer Nath, Anthony J. Olszanski, Patrick Ott, Aparna Priyanath Gupta, Merrick I. Ross, April K. Salama, Joseph Skitzki, Jeffrey Sosman, Susan M. Swetter, Kenneth K. Tanabe, Evan Wuthrick, Nicole R. McMillian, and Anita M. Engh
in greater detail subsequently. Immune Checkpoint Inhibitors Ipilimumab Ipilimumab, a monoclonal antibody that binds and blocks the function of the immune checkpoint receptor cytotoxic T lymphocyte antigen-4 (CTLA-4), has been shown to significantly
Sanam Loghavi, Mark J. Routbort, Keyur P. Patel, Rajyalakshmi Luthra, Wei-Lien Wang, Russell R. Broaddus, Michael A. Davies, and Alexander J. Lazar
therapy and monoclonal antibodies against CTLA-4, respectively, 44 – 46 and a subset of melanoma cases in which a specific genetic signature is linked to better response to ipilimumab. 47 In addition, increasing total mutational load of melanoma is
