The heterogeneity of the kinetics of response to ipilimumab in metastatic melanoma: Patient cases Journal Article


Authors: Saenger, Y. M.; Wolchok, J. D.
Article Title: The heterogeneity of the kinetics of response to ipilimumab in metastatic melanoma: Patient cases
Abstract: Cytotoxic T lymphocyte antigen-4 (CTLA-4) is a negative regulator of T-cell mediated immune responses and is the target of new antitumor immunotherapy strategies. Ipilimumab is a fully human, antagonistic monoclonal antibody directed against CTLA-4. Results from preclinical and early clinical trials support current phase II/III testing of ipilimumab as first- and second-line therapy for metastatic melanoma. Ipilimumab promotes durable objective responses and/or stable disease in patients with metastatic melanoma. Adverse events are medically manageable, largely immune-related, and presumably linked to the drug's mechanism of action. As more patients are treated with ipilimumab, it is becoming clear that the kinetics of responses are heterogeneous and significantly different from those of chemotherapy and other immunotherapy. Though objective response or stable disease is observed within 'conventional' time frames, responses have been observed weeks to months after therapy initiation. Response or stable disease may be preceded by apparent early disease progression, or may occur simultaneously with different progressing lesions within the same patient (a 'mixed' response). It is likely that the unique kinetics of response is a result of the time required to enhance and maintain an anti-tumor immune response to ipilimumab therapy. Consequently, patients may benefit from continued ipilimumab treatment through clinically known relevant disease progression or non-response during the full induction dosing schedule (12 weeks), without additional therapies. Understanding the kinetics of response to ipilimumab will help clinicians to manage patients who may benefit from treatment. In this article, several cases that illustrate the kinetics of response to ipilimumab are discussed. Copyright © 2008 by Jedd D. Wolchok.
Keywords: adult; clinical article; human tissue; treatment response; cancer surgery; surgical technique; unclassified drug; clinical feature; anamnesis; sorafenib; cisplatin; temozolomide; drug megadose; lymph node metastasis; glycoprotein gp 100; interleukin 2; ipilimumab; melanoma; metastasis; computer assisted tomography; multiple cycle treatment; skin biopsy; combination chemotherapy; vinblastine; monoclonal antibody; dyspnea; lymphocytopenia; rash; liver metastasis; needle biopsy; corticosteroid derivative; recurrent disease; physical examination; vaccine; case reports; monoclonal antibody alphavbeta3 integrin
Journal Title: Cancer Immunity
Volume: 8
ISSN: 1424-9634
Publisher: Academy of Cancer Immunology  
Date Published: 2008-01-17
Start Page: 1
Language: English
PROVIDER: scopus
PMCID: PMC2935787
PUBMED: 18198818
DOI/URL:
Notes: --- - "Cited By (since 1996): 5" - "Export Date: 17 November 2011" - "Source: Scopus"
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MSK Authors
  1. Jedd D Wolchok
    815 Wolchok