Checkpoint Inhibitors

Heinzerling L, De Toni EN, Schett G, Hundorfean G, Zimmer L (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Deutsches Ärzteblatt international Deutscher Ärzte-Verlag

Book Volume: 116

Pages Range: 119-126

Journal Issue: 8

DOI: 10.3238/arztebl.2019.0119

Abstract

BACKGROUND: Treatment with checkpoint inhibitors such as anti-programmed death-1 (anti-PD-1), anti-PD-ligand 1 (anti-PD-L1), and anti-cytotoxic T-lymphocyte antigen-4 (anti-CTLA-4) antibodies can prolong the survival of cancer patients, but it also induces autoimmune side effects in 86-96% of patients by activating the immune system. In 17-59% of patients, these are severe or even life-threatening. METHODS: This review is based on pertinent articles retrieved by a search in PubMed and on an evaluation of a side-effect registry. RESULTS: Checkpoint-inhibitor-induced autoimmune side effects manifest themselves in all organ systems, most commonly as skin lesions (46-62%), autoimmune colitis (22-48%), autoimmune hepatitis (7-33%), and endocrinopathies (thyroiditis, hypophysitis, adrenalitis, diabetes mellitus; 12-34%). Rarer side effects include pneumonitis (3-8%), nephritis (1-7%), cardiac side effects including cardiomyositis (5%), and neurological side effects (1-5%). Severe (sometimes lethal) side effects arise in 17-21%, 20-28%, and 59% of patients undergoing anti-PD-1 and anti- CTLA-4 antibody treatment and the approved combination therapy, respectively. With proper monitoring, however, these side effects can be recognized early and, usually, treated with success. Endocrine side effects generally require long-term hormone substitution. Patients who have stopped taking checkpoint inhibitors because of side effects do not show a poorer response of their melanoma or shorter survival in comparison to patients who continue to take checkpoint inhibitors. CONCLUSION: The complex management of checkpoint-inhibitor-induced side effects should be coordinated in experienced centers. The creation of an interdisciplinary "tox team" with designated experts for organ-specific side effects has proven useful. Prospective registry studies based on structured documentation of side effects in routine clinical practice are currently lacking and urgently needed.

Authors with CRIS profile

Lucie Heinzerling Department of Dermatology Georg Schett Lehrstuhl für Innere Medizin III

Involved external institutions

Universität Duisburg-Essen (UDE) DE Germany (DE) Ludwig-Maximilians-Universität (LMU) DE Germany (DE)

How to cite

APA:

Heinzerling, L., De Toni, E.N., Schett, G., Hundorfean, G., & Zimmer, L. (2019). Checkpoint Inhibitors. Deutsches Ärzteblatt international, 116(8), 119-126. https://doi.org/10.3238/arztebl.2019.0119

MLA:

Heinzerling, Lucie, et al. "Checkpoint Inhibitors." Deutsches Ärzteblatt international 116.8 (2019): 119-126.

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