Cited by 1,415Cancer Immunotherapy and BiomarkersImmunotherapy and Immune ResponsesCutaneous Melanoma Detection and Management

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Management of Immune-Related Adverse Events and Kinetics of Response With Ipilimumab

Weber, Jeffrey S., Kähler, Katharina C., Hauschild, Axel·2012·Journal of Clinical Oncology

DOI 10.1200/jco.2012.41.6750

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Abstract

Monoclonal antibodies directed against the immune checkpoint protein cytotoxic T-lymphocyte antigen-4 (CTLA-4; CD152)—ipilimumab and tremelimumab—have been investigated in metastatic melanoma and other cancers and have shown promising results. Recently, ipilimumab was approved by the US Food and Drug Administration for the treatment of metastatic melanoma. We review the literature on managing the adverse effects and kinetics of tumor regression with ipilimumab and provide guidelines on their management. During treatment with these antibodies, a unique set of adverse effects may occur, called immune-related adverse events (irAEs). These include rashes, which may rarely progress to life-threatening toxic epidermal necrolysis, and colitis, characterized by a mild to moderate, but occasionally also severe and persistent diarrhea. Hypophysitis, hepatitis, pancreatitis, iridocyclitis, lymphadenopathy, neuropathies, and nephritis have also been reported with ipilimumab. Early recognition of irAEs and initiation of treatment are critical to reduce the risk of sequelae. Interestingly, irAEs correlated with treatment response in some studies. Unique kinetics of response have been observed with CTLA-4 blockade with at least four patterns: (1) response in baseline lesions by week 12, with no new lesions seen; (2) stable disease, followed by a slow, steady decline in total tumor burden; (3) regression of tumor after initial increase in total tumor burden; and (4) reduction in total tumor burden during or after the appearance of new lesion(s) after week 12. We provide a detailed description of irAEs and recommendations for practicing oncologists who are managing them, along with the unusual kinetics of response associated with ipilimumab therapy.

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Authors: Weber, J. S., Kähler, K. C., & Hauschild, A.
Affiliations: Moffitt Cancer Center (US)
ORCID: Weber, Jeffrey S.
Kähler, Katharina C.
Hauschild, Axel
Venue: Journal of Clinical Oncology
Publisher: American Society of Clinical Oncology (ASCO)
Published: 2012-07-20
Volume: 30
Issue: 21
Pages: 2691-2697
ISSN: 0732-183X (ISSN-L)
1527-7755
DOI: 10.1200/jco.2012.41.6750
OpenAlex: W2109653150
Cited by: 1,415
References: 33
Citations by year: 2026: 24 · 2025: 35 · 2024: 59 · 2023: 79 · 2022: 84 · 2021: 117 · 2020: 129 · 2019: 123 · 2018: 146 · 2017: 153 · 2016: 152 · 2015: 145 · 2014: 94 · 2013: 65 · 2012: 9
FWCI: 10.34
Type: journal article
Language: en
Open access: closed
Locations: Journal of Clinical Oncology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
Keywords: ipilimumab, immune-related adverse events, CTLA-4 blockade, metastatic melanoma, immune checkpoint inhibitors, toxic epidermal necrolysis, colitis, hypophysitis, hepatitis, iridocyclitis, neuropathy, nephritis, adverse event management
MeSH terms: Ipilimumab, Antibodies, Monoclonal, Antineoplastic Agents, Colitis, Drug Eruptions, Diarrhea, Humans, Liver, Lymphatic Diseases, Melanoma, Mucous Membrane, Pancreatitis, Peripheral Nervous System Diseases, Pituitary Gland, Skin, Skin Neoplasms, Stevens-Johnson Syndrome, Uveitis, Scleritis, Chemical and Drug Induced Liver Injury, CTLA-4 Antigen, Antibodies, Monoclonal, Humanized

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Management of Immune-Related Adverse Events and Kinetics of Response With Ipilimumab

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