Immune checkpoint inhibitor colitis: the flip side of the wonder drugs

Naziheh Assarzadegan, Elizabeth Montgomery, Robert A Anders

Research output: Contribution to journalArticle

Abstract

Immune checkpoint inhibitors block the co-inhibitory receptors on T cells to activate their cytotoxic immune function and are rapidly being explored for the treatment of various advanced-stage malignancies. These novel drugs have already significantly increased survival rates. The first available immune checkpoint inhibitors were cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors (such as ipilimumab), followed by programmed cell death protein 1 (PD-1) and programmed cell death protein ligand 1 (PD-L1) inhibitors (such as pembrolizumab and nivolumab). Anti-PD-1 and anti-PD-L1 therapies have demonstrated better efficacy and tolerability and less severe adverse effects compared to anti-CTLA-4 agents. Idelalisib, a PI3Kδ isoform inhibitor, is another immunotherapeutic agent that is often classified separately and is currently used in treatment of chronic lymphocytic leukemia and non-Hodgkin lymphomas. Despite successful therapeutic responses, immune-related adverse events have been reported with the use of these agents. The gastrointestinal side effects, particularly diarrhea, are among the most commonly reported symptoms. The histologic features of immune checkpoint inhibitor-associated colitis show a spectrum of patterns of injury among various drug classes. There is significant overlap between immune checkpoint inhibitor-associated colitis and other colitides, making the differential diagnosis difficult—especially in the absence of clinical history. The histopathology data on immune checkpoint inhibitor-associated colitis are limited. Here we review clinical features as well as various histologic patterns of colitis associated with these groups of medications.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalVirchows Archiv
DOIs
StateAccepted/In press - Nov 15 2017

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Colitis
CD274 Antigen
CTLA-4 Antigen
Pharmaceutical Preparations
B-Cell Chronic Lymphocytic Leukemia
Programmed Cell Death 1 Receptor
Costimulatory and Inhibitory T-Cell Receptors
Phosphatidylinositol 3-Kinases
Non-Hodgkin's Lymphoma
Diarrhea
Protein Isoforms
Differential Diagnosis
Wounds and Injuries
Therapeutics
Neoplasms

Keywords

  • Colitis
  • Immune checkpoint inhibitors
  • PD-L1

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Cite this

Immune checkpoint inhibitor colitis : the flip side of the wonder drugs. / Assarzadegan, Naziheh; Montgomery, Elizabeth; Anders, Robert A.

In: Virchows Archiv, 15.11.2017, p. 1-9.

Research output: Contribution to journalArticle

Assarzadegan, Naziheh ; Montgomery, Elizabeth ; Anders, Robert A. / Immune checkpoint inhibitor colitis : the flip side of the wonder drugs. In: Virchows Archiv. 2017 ; pp. 1-9.
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