Management of side effects of immune checkpoint blockade by anti-CTLA-4 and anti-PD-1 antibodies in metastatic melanoma

Kaehler KC, Hassel JC, Heinzerling L, Loquai C, Moessner R, Ugurel S, Zimmer L, Gutzmer R (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Journal der Deutschen Dermatologischen Gesellschaft Wiley-Blackwell

Book Volume: 14

Pages Range: 662-81

Journal Issue: 7

DOI: 10.1111/ddg.13047

Abstract

CTLA-4 and PD-1 are potential targets for tumor-induced downregulation of lymphocytic immune responses. Immune checkpoint-modifying monoclonal antibodies oppose these effects, inducing T cell-mediated immune responses to various tumors including melanoma. Both anti-CTLA-4 and anti-PD-1 antibodies modify the interaction between tumor, antigen-presenting cells, and T lymphocytes. With respect to overall survival, clinical studies have shown a major benefit for the anti-CTLA-4 antibody ipilimumab as well as the two anti-PD-1 antibodies nivolumab and pembrolizumab. Following approval of ipilimumab in 2011, the latter two achieved market authorization in the summer of 2015. Immune responses thus induced and enhanced inevitably entail autoimmune phenomena, affecting various organs to varying degrees. Knowledge of these side effects is crucial with regard to prevention and management by treating physicians. Typically occurring early on and presenting with pronounced and persistent diarrhea, colitis represents a major and severe side effect. Other immune-mediated disorders include dermatitis, hypophysitis, thyroiditis, hepatitis, iridocyclitis as well as other less common autoimmune phenomena. Early recognition and initiation of treatment can reduce risks and sequelae for patients. This review describes the mechanisms of action of immune checkpoint blockade as well as its clinical effects in metastatic melanoma, with a detailed focus on the spectrum of adverse events and their therapeutic management.

Authors with CRIS profile

Lucie Heinzerling Department of Dermatology

Involved external institutions

Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) DE Germany (DE) Universitätsklinikum Heidelberg DE Germany (DE) Johannes Gutenberg-Universität Mainz (JGU) DE Germany (DE) Universitätsklinikum Göttingen DE Germany (DE) Universitätsklinikum Essen DE Germany (DE)

How to cite

APA:

Kaehler, K.C., Hassel, J.C., Heinzerling, L., Loquai, C., Moessner, R., Ugurel, S.,... Gutzmer, R. (2016). Management of side effects of immune checkpoint blockade by anti-CTLA-4 and anti-PD-1 antibodies in metastatic melanoma. Journal der Deutschen Dermatologischen Gesellschaft, 14(7), 662-81. https://doi.org/10.1111/ddg.13047

MLA:

Kaehler, Katharina C., et al. "Management of side effects of immune checkpoint blockade by anti-CTLA-4 and anti-PD-1 antibodies in metastatic melanoma." Journal der Deutschen Dermatologischen Gesellschaft 14.7 (2016): 662-81.

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