Impact of concurrent colonic CMV infection on clinical outcomes in immune checkpoint inhibitor-induced colitis

BACKGROUND AND AIMS: Immune checkpoint inhibitors (ICI) frequently trigger ICI-colitis, commonly leading to ICI discontinuation. With expanding ICI use, ICI-colitis is emerging as a significant clinical challenge. Cytomegalovirus (CMV) infection is known to occur in ICI-colitis, but its prevalence, risk factors and clinical impact are poorly defined. This study aimed to characterise the clinical trajectory of ICI-colitis patients with concurrent colonic CMV infection as compared to a CMV-negative colitis group.

METHODS: We retrospectively analysed consecutive ICI-treated patients with endoscopically and/or histologically confirmed ICI-colitis at two UK hospitals between 2015 and 2024. Clinical, endoscopic (Mayo Endoscopic Score, MES), treatment and oncologic outcome data were collected. CMV was identified by immunohistochemistry (IHC) on colonic biopsies. CMV-positive colitis cases were compared with CMV-negative colitis using chi- squared, Mann-Whitney U, and multivariable regression analyses.

RESULTS: Among 249 ICI-colitis patients, IHC proven CMV-positive colitis was detected in 21 (8.4%). CMV-positive colitis was associated with dual ICI therapy (OR 2.8, CI 1.06-7.15), prior infliximab exposure (OR 6.4, CI 2.56-16.7), bloody stool (OR 2.7, CI 1.05-6.69), and higher endoscopic severity (MES 2-3; OR 4.1, CI 1.60-10.38), despite similar CTCAE diarrhoea grades between groups. They also had a higher likelihood of requiring escalation to advanced therapy (80% vs 41.5%; OR 5.6, CI 1.96-15.74), with this association remaining significant after adjusting for endoscopic severity (p = 0.049). Colectomy rates were higher albeit low overall. Antiviral therapy did not significantly affect corticosteroid duration or recurrence, and CMV tissue status did not influence overall or progression-free survival.

CONCLUSION: Concurrent CMV-positive colitis occurs in a notable subset of ICI-colitis patients and may worsen disease severity, highlighting the importance of endoscopic biopsy, especially in steroid-refractory cases.