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Side effect management during immune checkpoint blockade using CTLA‐4 and PD‐1 antibodies for metastatic melanoma – an update
Author(s) -
Kähler Katharina C.,
Hassel Jessica C.,
Heinzerling Lucie,
Loquai Carmen,
Thoms KaiMartin,
Ugurel Selma,
Zimmer Lisa,
Gutzmer Ralf
Publication year - 2020
Publication title -
jddg: journal der deutschen dermatologischen gesellschaft
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.463
H-Index - 60
eISSN - 1610-0387
pISSN - 1610-0379
DOI - 10.1111/ddg.14128
Subject(s) - ipilimumab , nivolumab , medicine , ctla 4 , pembrolizumab , immunology , adverse effect , melanoma , immune system , immune checkpoint , blockade , antibody , immunotherapy , oncology , cancer research , t cell , receptor
Summary CTLA‐4 and PD‐1 play a key role in tumor‐induced downregulation of lymphocytic immune responses. Immune checkpoint inhibitors have been shown to alter the immune response to various cancer types. Anti‐CTLA‐4 and anti‐PD‐1 antibodies affect the interaction between tumor, antigen‐presenting cells and T lymphocytes. Clinical studies of the anti‐CTLA‐4 antibody ipilimumab and the anti‐PD‐1 antibodies nivolumab and pembrolizumab have provided evidence of their positive effects on overall survival in melanoma patients. Combined treatment using ipilimumab and nivolumab has been shown to achieve five‐year survival rates of 52 %. Such enhancement of the immune response is inevitably associated with adverse events. Knowledge of the spectrum of side effects is essential, both in terms of prevention and management. Adverse events include colitis, dermatitis, hypophysitis, thyroiditis, hepatitis and other, less common autoimmune phenomena. In recent years, considerable progress has been made in the detection and treatment of the aforementioned immune‐related adverse events. However, early diagnosis of rare neurological or cardiac side effects, which may be associated with increased mortality, frequently pose a challenge. The present update highlights our current understanding as well as new insights into the spectrum of side effects associated with checkpoint inhibitors and their management.