Checkpoint Inhibitor-Induced Colitis—A Clinical Overview of Incidence, Prognostic Implications and Extension of Current Treatment Options

Abstract

In recent years, anti-tumor immunotherapies have witnessed a major breakthrough with the emergence of immune checkpoint inhibitors (ICIs). However, the use of ICIs has also brought an era of a certain class of adverse events that differ from those of classical chemotherapies and are more reminiscent of autoimmune diseases. This article focuses exclusively on colitis as an irAE with emphasis on vulnerable patient groups, the prognostic significance of colitis, treatment, and new therapeutic approaches that may be applicable. Colitis itself is associated with a favorable oncological outcome of the underlying disease but is as well the most common irAE leading to discontinuation of therapy. Especially in vulnerable patient groups such as IBD patients and elderly patients, colitis occurs more frequently as a side effect. It is precisely in these two patient groups that side effects more often lead to discontinuation of therapy. Therefore, in addition to the current therapy of colitis through immunosuppression, the focus should also be on new forms of therapy of severe colitis, such as fecal transplantation or ileostomy creation.

Bridging the Gap: Connecting the Mechanisms of Immune-Related Adverse Events and Autoimmunity Through PD-1

“…Gastrointestinal irAEs include mucositis, aphthous ulcers, gastritis, abdominal pain, and colitis. ICI-induced colitis occurs most frequently following combined inhibition of PD-1 and CTLA-4, with some reporting incidence of up to 32% ( Zhang et al, 2018 ; Najjar et al, 2020 ; Portenkirchner et al, 2021 ). Interestingly, the rate of incidence may be influenced by the type of cancer being treated ( Wang et al, 2017a ; Portenkirchner et al, 2021 ).…”

“…ICI-induced colitis occurs most frequently following combined inhibition of PD-1 and CTLA-4, with some reporting incidence of up to 32% ( Zhang et al, 2018 ; Najjar et al, 2020 ; Portenkirchner et al, 2021 ). Interestingly, the rate of incidence may be influenced by the type of cancer being treated ( Wang et al, 2017a ; Portenkirchner et al, 2021 ). On histological examination, the features of ICI-induced colitis are similar to acute colitis with cryptitis, intraepithelial neutrophilic lymphocytes, mucosal ulcerations, crypt abscesses, and apoptosis ( Berman et al, 2010 ; Verschuren et al, 2016 ; Adler et al, 2018 ; Geukes Foppen et al, 2018 ; Bellaguarda and Hanauer, 2020 ; Chen et al, 2020 ; Hayashi et al, 2021 ; Portenkirchner et al, 2021 ).…”

“…Interestingly, the rate of incidence may be influenced by the type of cancer being treated ( Wang et al, 2017a ; Portenkirchner et al, 2021 ). On histological examination, the features of ICI-induced colitis are similar to acute colitis with cryptitis, intraepithelial neutrophilic lymphocytes, mucosal ulcerations, crypt abscesses, and apoptosis ( Berman et al, 2010 ; Verschuren et al, 2016 ; Adler et al, 2018 ; Geukes Foppen et al, 2018 ; Bellaguarda and Hanauer, 2020 ; Chen et al, 2020 ; Hayashi et al, 2021 ; Portenkirchner et al, 2021 ). In patients with metastatic melanoma that were given ICI therapy that included anti–CTLA-4, an increased number if IL-17A–secreting CD4 T-cells (T H 17) was observed in peripheral circulation of those who developed colitis ( von Euw et al, 2009 ; Anderson et al, 2019 ).…”

Pharmacological Treatments Available for Immune-Checkpoint-Inhibitor-Induced Colitis

“…An association between irAE colitis and prognosis in several cancers has been reported [ 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. Masuda et al [ 19 ] reported significantly longer overall survival (OS) and progression-free survival (PFS) in patients with gastric cancer receiving nivolumab with the onset of irAE colitis than in those without it.…”

Immune Checkpoint Inhibitor-Associated Colitis: From Mechanism to Management

“…Prior studies have demonstrated the incidence, risk factors, diagnosis, and management of CIC (24)(25)(26)(27)(28)(29). Nonetheless, they have variable concentrations and orientations, which are complementary but not deep and comprehensive.…”