Diverse types of dermatologic toxicities from immune checkpoint blockade therapy

Immunomodulatory drugs that leverages host immune mechanisms to destroy tumor cells have been met with great promise in the treatment of cancer. Immunotherapy, targeting cytotoxic T‐lymphocyte‐associated antigen 4 (CTLA‐4) and the programmed cell death 1 (PD‐1) receptor and its ligand (PD‐L1) have s...

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Bibliographic Details
Published in:Journal of cutaneous pathology 2017-02, Vol.44 (2), p.158-176
Main Authors: Curry, Jonathan L., Tetzlaff, Michael T., Nagarajan, Priyadharsini, Drucker, Carol, Diab, Adi, Hymes, Sharon R., Duvic, Madeleine, Hwu, Wen‐Jen, Wargo, Jennifer A., Torres‐Cabala, Carlos A., Rapini, Ronald P., Prieto, Victor G.
Format: Article
Language:English
Subjects:
Antibodies, Monoclonal - adverse effects
Antibodies, Monoclonal, Humanized - adverse effects
Antineoplastic Agents - adverse effects
anti‐CTLA‐4
anti‐PD‐1
anti‐PD‐L1
Apoptosis
Bullous pemphigoid
Cancer
Cancer immunotherapy
Cell death
CTLA-4 protein
Cytotoxicity
Dermatitis
dermatologic toxicities
Drug Eruptions - etiology
Drug Eruptions - pathology
Humans
Immune checkpoint
immune checkpoint antibody
Immunomodulation
Immunosuppressive agents
Immunotherapy
Inflammation
Ipilimumab
Keratinocytes
Lymphocytes T
Melanocytes
Nivolumab
PD-1 protein
PD-L1 protein
Solid tumors
Toxicity
Tumor cells
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Summary:Immunomodulatory drugs that leverages host immune mechanisms to destroy tumor cells have been met with great promise in the treatment of cancer. Immunotherapy, targeting cytotoxic T‐lymphocyte‐associated antigen 4 (CTLA‐4) and the programmed cell death 1 (PD‐1) receptor and its ligand (PD‐L1) have shown tremendous improvements in the survival of patients with advanced solid tumors. However, the development of dermatologic toxicity (DT) is a consequence to immunotherapy. Review of published reports of the DT to immunotherapy revealed patients receiving anti‐CTCLA‐4 antibody or anti‐PD‐1/PD‐L1 antibody often develop a DT of any type and grade. In this article, of the 3825 patients who were treated with anti‐PD‐1 and of 556 patients receiving anti‐PD‐L1, DT of any type and grade were reported in 1474 (∼39%) and 95 (∼17%) of patients, respectively. The emergence of specific types of DT to immunotherapy is beginning to be recognized can be categorized into four groups: (a) inflammatory, (b) immunobullous, (c) alteration of keratinocytes and (d) alteration of melanocytes. Lichenoid dermatitis and bullous pemphigoid appear to be DT more associated with anti‐PD‐1/PD‐L1 antibody. The DT profile in patients receiving immunotherapy is diverse, and early recognition of specific types of DT that clinicians may encounter is critical for optimal patient care
ISSN:0303-6987
1600-0560
DOI:10.1111/cup.12858