The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
Management of Immune-Related Adverse Events and Kinetics of Response With Ipilimumab
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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“We observed an association between irAEs and improved PFS using a landmark analysis, in agreement with previous studies58–60, and uncovered that baseline gut microbiome composition segregated PD-1-treated patients who developed irAEs from those who did not.”
From Intestinal microbiota signatures of clinical response and immune-related adverse events in melanoma patients treated with anti-PD-1 (2022) · cites this paper as [60]
Citations
Cites
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma
Hodi, F. S., O'Day, S. J., McDermott, D. F., Weber, R. W., Sosman, J. A., Haanen, J. B., Gonzalez, R., Robert, C., Schadendorf, D., Hassel, J. C., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1003466 · Cited by 15,155
Self-citationIpilimumab plus Dacarbazine for Previously Untreated Metastatic Melanoma
Robert, C., Thomas, L., Bondarenko, I., O'Day, S., Weber, J., Garbe, C., Lebbe, C., Baurain, J.-F., Testori, A., Grob, J.-J., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1104621 · Cited by 4,496
Self-citationWolchok, J. D., Hoos, A., O'Day, S. J., Weber, J. S., Hamid, O., Lebbé, C., Maio, M., Binder, M., Bohnsack, O., Nichol, G. M., et al. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-1624 · Cited by 3,214
Self-citationTivol, E. A., Borriello, F., Schweitzer, A. N., Lynch, W. P., Bluestone, J. A., & Sharpe, A. H. (1995) · Immunity · doi:10.1016/1074-7613(95)90125-6 · Cited by 2,914
Lymphoproliferative Disorders with Early Lethality in Mice Deficient in Ctla-4
Waterhouse, P., Penninger, J. M., Timms, E., Wakeham, A., Shahinian, A., Lee, K. P., Thompson, C. B., Griesser, H., & Mak, T. W. (1995) · Science · doi:10.1126/science.270.5238.985 · Cited by 2,766
Greenwald, R. J., Freeman, G. J., & Sharpe, A. H. (2005) · Annual Review of Immunology · doi:10.1146/annurev.immunol.23.021704.115611 · Cited by 2,318
Phan, G. Q., Yang, J. C., Sherry, R. M., Hwu, P., Topalian, S. L., Schwartzentruber, D. J., Restifo, N. P., Haworth, L. R., Seipp, C. A., Freezer, L. J., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1533209100 · Cited by 1,575
Wolchok, J. D., Neyns, B., Linette, G., Negrier, S., Lutzky, J., Thomas, L., Waterfield, W., Schadendorf, D., Smylie, M., Guthrie, T., et al. (2010) · The Lancet Oncology · doi:10.1016/s1470-2045(09)70334-1 · Cited by 1,195
Attia, P., Phan, G. Q., Maker, A. V., Robinson, M. R., Quezado, M. M., Yang, J. C., Sherry, R. M., Topalian, S. L., Kammula, U. S., Royal, R. E., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.06.205 · Cited by 1,012
Hodi, F. S., Mihm, M. C., Soiffer, R. J., Haluska, F. G., Butler, M., Seiden, M. V., Davis, T., Henry-Spires, R., MacRae, S., Willman, A., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0830997100 · Cited by 1,006
Research works printed but not linked: 5
- Lebbé C, Presented at Perspectives in Melanoma XII, Scheveningen/the Hague, the Netherlands
- Weber JS, 2009, J Clin Oncol, 27, 466s
- Saenger YM, 2008, Cancer Immun, 8, 1
- Pennock GK, 2011, Am J Clin Oncol
- Yuan J, 2010, Cancer Immun, 10, 1
Cited by
Sorted by citations
Pembrolizumab versus Ipilimumab in Advanced Melanoma
Robert, C., Schachter, J., Long, G. V., Arance, A., Grob, J. J., Mortier, L., Daud, A., Carlino, M. S., McNeil, C., Lotem, M., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1503093 · Cited by 5,887
Immune-Related Adverse Events Associated with Immune Checkpoint Blockade
Postow, M. A., Sidlow, R., & Hellmann, M. D. (2018) · New England Journal of Medicine · doi:10.1056/nejmra1703481 · Cited by 4,849
Brahmer, J. R., Lacchetti, C., Schneider, B. J., Atkins, M. B., Brassil, K. J., Caterino, J. M., Chau, I., Ernstoff, M. S., Gardner, J. M., Ginex, P., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2017.77.6385 · Cited by 3,713
“Among the diverse irAEs, cutaneous toxicities such as rash, pruritus, and vitiligo are by far the most common and the earliest to occur.(5) Although most cutaneous toxicities are transient, they can cause significant morbidity and impairment of patients’ health-related quality of life.”
BackgroundSelf-citationImmune Checkpoint Blockade in Cancer Therapy
Postow, M. A., Callahan, M. K., & Wolchok, J. D. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2014.59.4358 · Cited by 2,782
Weber, J. S., D’Angelo, S. P., Minor, D. R., Hodi, F. S., Gutzmer, R., Neyns, B., Höeller, C., Khushalani, N. I., Miller, W. H., Lao, C. D., et al. (2015) · The Lancet Oncology · doi:10.1016/s1470-2045(15)70076-8 · Cited by 2,725
Self-citation
Metadata
- Authors
- Weber, J. S., Kähler, K. C., & Hauschild, A.
- Affiliations
- Moffitt Cancer Center (US)
- Venue
- Journal of Clinical Oncology
- Published
- 2012-07-20
- Volume
- 30
- Issue
- 21
- Pages
- 2691-2697
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- 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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