Home LiteratureArticle Details
PMID: 25659583 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Review of immune-related adverse events in prostate cancer patients treated with ipilimumab: MD Anderson experience.

Oncogene ·Vol. 34 ·No. 43 ·2015-10-00 ·Pages 5411-7

Gao J, He Q, Subudhi S, Aparicio A, Zurita-Saavedra A, Lee DH, Jimenez C, Suarez-Almazor M, Sharma P

Abstract

Targeting a T-cell inhibitory checkpoint with the anti-CTLA-4 monoclonal antibody, ipilimumab, represents a scientific breakthrough in immunotherapy for the treatment of cancer. However, ipilimumab therapy is also associated with unique side effects, known as immune-related adverse events (irAEs), which need to be recognized and managed with immunosuppressive agents. To date, the majority of our knowledge regarding ipilimumab-associated side effects is based upon clinical studies in melanoma. Here we provide a review of ipilimumab-induced irAEs and our experience in a cohort of 44 patients with prostate cancer who were treated at the MD Anderson Cancer Center on two different clinical trial protocols.

MeSH Terms
Animals Antibodies, Monoclonal/adverse effects,immunology,pharmacology,therapeutic use Humans Immunotherapy/methods Ipilimumab Male Prostatic Neoplasms/drug therapy,immunology
Chemicals
Antibodies, Monoclonal Ipilimumab
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Gao J
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
He Q
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Subudhi S
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Aparicio A
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Zurita-Saavedra A
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Lee D H
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jimenez C
Department of Endocrine Neoplasia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Suarez-Almazor M
Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Sharma P
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. | Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
References (40)
40 references, click to expand
  1. Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomised, double-blind, multicentre, phase 2, dose-ranging study.
    Lancet Oncol. 2010 Feb;11(2):155-64 PMID: 20004617
  2. Anti-CTLA4 antibody-induced lupus nephritis.
    N Engl J Med. 2009 Jul 9;361(2):211-2 PMID: 19587352
  3. CTLA4 blockade increases Th17 cells in patients with metastatic melanoma.
    J Transl Med. 2009;7:35 PMID: 19457253
  4. Enterocolitis in patients with cancer after antibody blockade of cytotoxic T-lymphocyte-associated antigen 4.
    J Clin Oncol. 2006 May 20;24(15):2283-9 PMID: 16710025
  5. Combined immunotherapy with granulocyte-macrophage colony-stimulating factor-transduced allogeneic prostate cancer cells and ipilimumab in patients with metastatic castration-resistant prostate cancer: a phase 1 dose-escalation trial.
    Lancet Oncol. 2012 May;13(5):509-17 PMID: 22326922
  6. Anti-IL-17 mAbs herald new options in psoriasis.
    Nat Biotechnol. 2012 Jun;30(6):475-7 PMID: 22678368
  7. Management of immune-related adverse events and kinetics of response with ipilimumab.
    J Clin Oncol. 2012 Jul 20;30(21):2691-7 PMID: 22614989
  8. Hemophilia A induced by ipilimumab.
    N Engl J Med. 2011 Nov 3;365(18):1747-8 PMID: 22047582
  9. Cutting edge: CTLA-4--B7 interaction suppresses Th17 cell differentiation.
    J Immunol. 2010 Aug 1;185(3):1375-8 PMID: 20601598
  10. Anti-CTLA-4 antibody-induced Guillain-Barré syndrome in a melanoma patient.
    Ann Oncol. 2011 Apr;22(4):991-3 PMID: 21357649
  11. CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation.
    J Exp Med. 1995 Aug 1;182(2):459-65 PMID: 7543139
  12. Blockade of cytotoxic T-lymphocyte antigen-4 by ipilimumab results in dysregulation of gastrointestinal immunity in patients with advanced melanoma.
    Cancer Immun. 2010;10:11 PMID: 21090563
  13. Concurrent decrease in IL-10 with development of immune-related adverse events in a patient treated with anti-CTLA-4 therapy.
    Cancer Immun. 2008;8:9 PMID: 18503261
  14. Immunologic correlates of the abscopal effect in a patient with melanoma.
    N Engl J Med. 2012 Mar 8;366(10):925-31 PMID: 22397654
  15. Enhancement of antitumor immunity by CTLA-4 blockade.
    Science. 1996 Mar 22;271(5256):1734-6 PMID: 8596936
  16. Autoimmunity in a phase I trial of a fully human anti-cytotoxic T-lymphocyte antigen-4 monoclonal antibody with multiple melanoma peptides and Montanide ISA 51 for patients with resected stages III and IV melanoma.
    J Clin Oncol. 2005 Feb 1;23(4):741-50 PMID: 15613700
  17. Ipilimumab and a poxviral vaccine targeting prostate-specific antigen in metastatic castration-resistant prostate cancer: a phase 1 dose-escalation trial.
    Lancet Oncol. 2012 May;13(5):501-8 PMID: 22326924
  18. Development of ipilimumab: a novel immunotherapeutic approach for the treatment of advanced melanoma.
    Ann N Y Acad Sci. 2013 Jul;1291:1-13 PMID: 23772560
  19. Cytotoxic T-lymphocyte-associated antigen-4 blockage can induce autoimmune hypophysitis in patients with metastatic melanoma and renal cancer.
    J Immunother. 2005 Nov-Dec;28(6):593-8 PMID: 16224277
  20. Expression and function of CTLA-4 in Th1 and Th2 cells.
    J Immunol. 1998 Oct 1;161(7):3347-56 PMID: 9759851
  21. CTLA-4 blockade enhances polyfunctional NY-ESO-1 specific T cell responses in metastatic melanoma patients with clinical benefit.
    Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20410-5 PMID: 19074257
  22. Improved survival with ipilimumab in patients with metastatic melanoma.
    N Engl J Med. 2010 Aug 19;363(8):711-23 PMID: 20525992
  23. Cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma: a new cause of uveitis.
    J Immunother. 2004 Nov-Dec;27(6):478-9 PMID: 15534492
  24. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma.
    N Engl J Med. 2011 Jun 30;364(26):2517-26 PMID: 21639810
  25. Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma.
    Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8372-7 PMID: 12826605
  26. Anti-CTLA-4 antibody therapy associated autoimmune hypophysitis: serious immune related adverse events across a spectrum of cancer subtypes.
    Pituitary. 2010;13(1):29-38 PMID: 19639414
  27. Ipilimumab and its toxicities: a multidisciplinary approach.
    Oncologist. 2013 Jun;18(6):733-43 PMID: 23774827
  28. CTLA4 blockade and GM-CSF combination immunotherapy alters the intratumor balance of effector and regulatory T cells.
    J Clin Invest. 2006 Jul;116(7):1935-45 PMID: 16778987
  29. Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients.
    Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4712-7 PMID: 12682289
  30. Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: a multicenter single-arm phase II study.
    Ann Oncol. 2010 Aug;21(8):1712-7 PMID: 20147741
  31. Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial.
    Lancet Oncol. 2014 Jun;15(7):700-12 PMID: 24831977
  32. The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network.
    PLoS One. 2013;8(1):e53745 PMID: 23341990
  33. Skin reactions in a subset of patients with stage IV melanoma treated with anti-cytotoxic T-lymphocyte antigen 4 monoclonal antibody as a single agent.
    Arch Dermatol. 2006 Feb;142(2):166-72 PMID: 16490844
  34. Immune-mediated adverse events associated with ipilimumab ctla-4 blockade therapy: the underlying mechanisms and clinical management.
    Scientifica (Cairo). 2013;2013:857519 PMID: 24278787
  35. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion.
    Nat Med. 2002 Aug;8(8):793-800 PMID: 12091876
  36. Thyroid autoimmunity and ophthalmopathy related to melanoma biological therapy.
    Eur J Endocrinol. 2011 Feb;164(2):303-7 PMID: 21088057
  37. SPAS-1 (stimulator of prostatic adenocarcinoma-specific T cells)/SH3GLB2: A prostate tumor antigen identified by CTLA-4 blockade.
    Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3509-14 PMID: 18303116
  38. Melan-A-specific cytotoxic T cells are associated with tumor regression and autoimmunity following treatment with anti-CTLA-4.
    Clin Cancer Res. 2009 Apr 1;15(7):2507-13 PMID: 19318477
  39. Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma.
    J Exp Med. 2013 Aug 26;210(9):1695-710 PMID: 23897981
  40. Inflammatory enteric neuropathy with severe constipation after ipilimumab treatment for melanoma: a case report.
    J Immunother. 2009 Feb-Mar;32(2):203-5 PMID: 19238020
Article Info
Journal
Oncogene
Abbr.
Oncogene
ISSN
1476-5594
DOI
10.1038/onc.2015.5
Published
2015-10-00
Epub
2015-00-09
Pages
5411-7
Language
English
Region
England
NLM ID
8711562
PMCID
PMC4530091
Subset
IM
Grants
NCI NIH HHS · R01 CA163793 · United States
NCI NIH HHS · 1-R01 CA1633793-01 · United States
External Links
PubMed source DOI: 10.1038/onc.2015.5 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2