Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2013 Oct;15(5):500-8.
doi: 10.1007/s11912-013-0337-1.

Checkpoint modulation in melanoma: an update on ipilimumab and future directions

David B Page  1 , Michael A Postow, Margaret K Callahan, Jedd D Wolchok
Affiliations
Review

Checkpoint modulation in melanoma: an update on ipilimumab and future directions

David B Page et al. Curr Oncol Rep. 2013 Oct.

Abstract

Ipilimumab, an anti-cytotoxic T-lymphocyte antigen 4 antibody, was the first therapy demonstrated to improve overall survival in melanoma. Since ipilimumab's approval by the FDA in 2011, a wealth of data has amassed, helping clinicians to optimize its use. We have learned how to mitigate the adverse effects of ipilimumab, identified its effects in melanoma subpopulations such as those with brain metastases, uveal melanoma, and mucosal melanoma, discovered potential biomarkers of activity, and investigated its use in combination with other therapeutic modalities. These discoveries have paved the way for rapid development of second-generation immunomodulatory antibodies such as inhibitors of the programmed cell death 1 receptor axis. These new agents hold promise as monotherapy, but perhaps the greatest allure lies in the possibility of combining these agents in synergistic multidrug regimens.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest

Margaret K. Callahan has received a research grant from Bristol-Myers Squibb.

Michael A. Postow has served on a nonpaid advisory board for Bristol-Myers Squibb and has received a research grant and travel reimbursement from Bristol-Myers Squibb.

Jedd D. Wolchok has been a consultant for Bristol-Myers Squibb and Merck, has received grants from Bristol-Myers Squibb, Merck, and AstraZeneca, and has received travel accommodation from Bristol-Myers Squibb.

David B. Page declares no conflict of interest.

Figures

Fig. 1
Fig. 1
Therapeutic targets for immunoregulatory antibodies. GITR glucocorticoid-induced tumor necrosis factor receptor related protein, NK cell natural killer cell, KIR killer inhibitory receptor, LAG-3 lymphocyte activation gene 3, TIM-3 T-cell immunoglobulin- and mucin-domain containing 3, CTLA-4 cytotoxic T lymphocyte antigen 4, BTLA B- and T-cell attenuator; PD-1 programmed cell death 1, PD-L1 programmed cell death 1 ligand 1
See this image and copyright information in PMC

References

    1. Atkins MB, Lotze MT, Dutcher JP, et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol. 1999;17(7):2105–16. - PubMed
    1. Serrone L, Zeuli M, Sega FM, Cognetti F. Dacarbazine-based chemotherapy for metastatic melanoma: thirty-year experience overview. J Exp Clin Cancer Res. 2000;19(1):21–34. - PubMed
    1. Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–23. This was the first phase III study to demonstrate an overall survival benefit with therapy in metastatic melanoma. - PMC - PubMed
    1. Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011;364(26):2517–26. This is a phase III study showing improved overall survival with ipilimumab plus dacarbazine compared with a previous standard of care, dacarbazine. - PubMed
    1. Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364(26):2507–16. This is a phase III trial establishing vemurafenib as a standard of care for metastatic melanoma patients harboring the V600E BRAF mutation. - PMC - PubMed

MeSH terms