Abstract
Therapeutic reversal of immune tolerance following immune checkpoint inhibitors (ICPI)
administration, has proven effective in prolonging survival of patients with a variety
of solid and liquid tumors, often however at the expenses of discrete toxicities known
as immune-related adverse events (AEs). Such reactions result from activation of the
immune system and often present with generalized symptoms including fatigue or fever
and, in some patients, may cause organ-specific damage. Skin, gut, endocrine, lung
and musculoskeletal are the most frequent targets of ICPI toxicity whereas, cardiovascular,
hematologic, renal, neurologic and ophthalmologic AEs occur much less frequently.
While the majority of AEs are mild to moderate, serious, occasionally life-threatening
reactions have been reported, including severe colitis, pneumonitis, encephalitis,
toxic epidermal necrolysis, myocarditis, and diabetic ketoacidosis, with a death toll
of 2%. Hepatocellular carcinoma (HCC) is becoming an attractive area for immunotherapy.
Owing to the fact that the association of HCC with cirrhosis may jeopardize tolerability
of ICPI therapy, attention has been paid to identifying, preventing, and treating
the AEs associated with ICPI, with a focus on liver safety. Though in most studies
AEs resolved with interruption of treatment and short course of steroids, identification
of predictive biomarkers of response might help sparing patients from potentially
life-threatening toxicity in the absence of clinical benefit.
Keywords
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Article info
Publication history
Published online: July 08, 2019
Accepted:
June 19,
2019
Received:
April 16,
2019
Identification
Copyright
© 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
ScienceDirect
Access this article on ScienceDirectLinked Article
- Immunotherapy for hepatocellular carcinoma: A review of potential new drugs based on ongoing clinical studies as of 2019Digestive and Liver DiseaseVol. 51Issue 8
- PreviewIn the latest years, antineoplastic immunotherapy revolutionised the therapeutic landscape in oncology. First shown to be effective in melanoma and non-small cell lung carcinoma, immune checkpoint inhibitors are now being tested for the treatment of hepatocellular carcinoma (HCC). Preliminary results have been particularly promising. As a consequence, an increasing number of clinical trials are underway. The role of the immune system in carcinogenesis (with particular reference to tumour escape immune mechanisms), as well as the current immunotherapy trials for HCC in its different clinical scenarios, are the subject of this review.
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