Advanced Therapies for the Management of Immune Checkpoint Inhibitor-Induced Colitis

Immune checkpoint inhibitors (ICIs), including anti-CTLA-4, anti-PD-1, and anti-PD-L1 agents, have revolutionized cancer therapy by enhancing T-cell–mediated antitumor responses and significantly improving survival across multiple malignancies. Despite these advances, ICIs are associated with immune-related adverse events (irAEs), with ICI-induced colitis representing one of the most common and severe gastrointestinal toxicities. Clinically and histopathologically, this condition often resembles inflammatory bowel disease (IBD) and can substantially impact treatment continuity and patient quality of life. Corticosteroids remain the standard first-line therapy; however, up to one-third of patients exhibit steroid-refractory disease or develop significant steroid-related toxicity, highlighting the need for alternative therapeutic strategies. Biologic agents, particularly infliximab and vedolizumab, have demonstrated high efficacy in this setting, with infliximab associated with more rapid symptom control and vedolizumab offering a favorable steroid-sparing profile. In patients with multi-refractory disease, additional agents such as ustekinumab, tofacitinib, and tocilizumab have shown promise, although current evidence is limited and primarily derived from small studies and case series. This review critically examines current treatment paradigms for ICI-induced colitis, focusing on efficacy, safety, and potential implications for oncologic outcomes. Despite increasing use of advanced therapies, clinical decision-making remains largely guided by retrospective data, and key uncertainties persist regarding optimal treatment sequencing, patient selection, and long-term safety. Future research should prioritize prospective randomized trials incorporating both oncologic and gastrointestinal endpoints, as well as mechanistic studies aimed at identifying predictive biomarkers and therapeutic targets that preserve anti-tumor immunity.

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Publication Details

Journal
Cancers
Published
2026-09-24
DOI
https://doi.org/10.3390/cancers18193108
Primary Topic
Cancer Immunotherapy and Biomarkers
Type
article
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article

Advanced Therapies for the Management of Immune Checkpoint Inhibitor-Induced Colitis

Luca Albarello, Alessandra Zilli, Ferdinando D’Amico, Laurent Peyrin‐Biroulet et al.
Cancers
Cancer Immunotherapy and Biomarkers
article

Advanced Therapies for the Management of Immune Checkpoint Inhibitor-Induced Colitis

Luca Albarello, Alessandra Zilli, Ferdinando D’Amico, Laurent Peyrin‐Biroulet, Sara Oresti, Mariangela Allocca, Roberto Ferrara, Fabrizio Fanizzi, Cosimo Simone Matichecchia, Silvio Danese
article en

Abstract

Immune checkpoint inhibitors (ICIs), including anti-CTLA-4, anti-PD-1, and anti-PD-L1 agents, have revolutionized cancer therapy by enhancing T-cell–mediated antitumor responses and significantly improving survival across multiple malignancies. Despite these advances, ICIs are associated with immune-related adverse events (irAEs), with ICI-induced colitis representing one of the most common and severe gastrointestinal toxicities. Clinically and histopathologically, this condition often resembles inflammatory bowel disease (IBD) and can substantially impact treatment continuity and patient quality of life. Corticosteroids remain the standard first-line therapy; however, up to one-third of patients exhibit steroid-refractory disease or develop significant steroid-related toxicity, highlighting the need for alternative therapeutic strategies. Biologic agents, particularly infliximab and vedolizumab, have demonstrated high efficacy in this setting, with infliximab associated with more rapid symptom control and vedolizumab offering a favorable steroid-sparing profile. In patients with multi-refractory disease, additional agents such as ustekinumab, tofacitinib, and tocilizumab have shown promise, although current evidence is limited and primarily derived from small studies and case series. This review critically examines current treatment paradigms for ICI-induced colitis, focusing on efficacy, safety, and potential implications for oncologic outcomes. Despite increasing use of advanced therapies, clinical decision-making remains largely guided by retrospective data, and key uncertainties persist regarding optimal treatment sequencing, patient selection, and long-term safety. Future research should prioritize prospective randomized trials incorporating both oncologic and gastrointestinal endpoints, as well as mechanistic studies aimed at identifying predictive biomarkers and therapeutic targets that preserve anti-tumor immunity.

CancersVol. 18(19)
Vita-Salute San Raffaele University (IT), IRCCS Ospedale San Raffaele (IT), Northwestern Medicine (US)
Peace, Justice and strong institutions
Openalex Percentile: Top 14%
Cancer Immunotherapy and Biomarkers
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