Abstract
Immune checkpoint inhibitors (ICIs) are currently an important component of the standard first-line treatment for many neoplasms. Some guidelines recommend ICIs as adjuvant treatment. With their increased use, the incidence of associated immune-mediated adverse reactions will also increase. A significant proportion of these reactions is represented by immune-mediated diarrhea or colitis, hepatitis, and immune-mediated pancreatic damage. The present review aims to highlight the new trends related to the diagnosis and treatment of these adverse effects depending on their degree, from the perspective of the gastroenterologist. To accomplish this, a literature search was performed, and 30 publications were considered relevant (according to the Population, Intervention, Comparison, Outcomes, and Study [PICOS] criteria). The information about each of the three toxicities in this paper was structured in two categories such as differential diagnosis and treatment. This review aims not only to increase awareness of these side effects in the gastroenterology community but also to promote the development of new treatment guidelines with contributions from gastroenterologists.
Highlights
Immune checkpoint inhibitors (ICIs), which are most often represented by cytotoxic T-lymphocyteassociated protein 4 (CTLA-4) inhibitors, programmed cell death protein-1 (PD-1) inhibitors, and programmed cell death protein-1 ligand (PD-L1) inhibitors, have special importance in oncological treatment
They can be administrated alone or in combination with another ICI, with immunotherapy, and even with radiation therapy. Their mechanism of action is that they make tumor cells visible to the immune system, which can lead to immune-mediated adverse reactions
ICIs are becoming an increasingly important component in systemic oncological treatment, and they can be administered in almost all types of solid tumors
Summary
Immune checkpoint inhibitors (ICIs), which are most often represented by cytotoxic T-lymphocyteassociated protein 4 (CTLA-4) inhibitors, programmed cell death protein-1 (PD-1) inhibitors, and programmed cell death protein-1 ligand (PD-L1) inhibitors, have special importance in oncological treatment. For moderate increases in transaminases (three to five times higher than the normal values), the patient will be closely monitored, immunotherapy will be discontinued, and prednisone at a dose of 0.5-1 mg/kg/day will be considered. At values consistent with grade 3 toxicity (five times higher but 20 times lower than the normal values), the patient will be admitted to inpatient care, immunotherapy will be discontinued, and 1-2-mg/kg/day prednisone therapy (or equivalent) will be initiated. Discontinue ICIs. Methylprednisolone at 2 mg/kg/day, monitor for 2 days → if no improvement, start mycophenolate mofetil at 1000 mg three times daily → if no improvement under double immunosuppression, consider administering anti-thymocyte globulin or tacrolimus. Better outcomes in treating immune-induced toxicity will emerge with the accumulation of experience by gastroenterologists [29]
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