Incidence of immune checkpoint inhibitor–mediated diarrhea and colitis (imDC) in patients with cancer and preexisting inflammatory bowel disease: a propensity score–matched retrospective study

Abstract

Background and aimsThe risk of use of immune-mediated diarrhea and colitis (imDC) in patients with preexisting inflammatory bowel disease (IBD) is not fully understood. We report the incidence of imDC in these patients, and compare with a matched cohort of patients with cancer and without IBD.MethodsPatients with IBD from a tertiary center cancer registry who underwent immune checkpoint inhibitor (ICI) therapy from 2011 to 2019 were identified. A 1:5 matched cohort of patients with and without a history of IBD was created, based on age, ICI therapy, and cancer type. Demographic data, clinical history of IBD, cancer, ICI agent, imDC events after ICI therapy, and overall survival were analyzed. Overall survival and time-to-imDC (TTimDC) were estimated by Kaplan-Meier and multivariate Cox proportional-hazards models.ResultsFrom a retrospective cohort of 3900 patients who received ICI therapy, 30 patients with IBD were matched with 150 patients without a history of IBD. Most patients received PD-1/PD-L1 inhibitor monotherapy (154/180, 85.6%). Individuals with preexisting IBD showed significantly shorter TTimDC than those in the non-IBD group (1-year imDC-free rate 67% vs 93%; HR 7.59, 95% CI 3.00 to 19.15, p<0.0001). Eleven (36%) from the IBD cohort experienced imDC events; none led to life-threatening conditions needing surgical interventions or death. Corticosteroids or biologics were needed in 8/11 (73%) patients, and discontinuation of therapy improved imDC in the remaining three. Half of patients required hospitalization. In contrast, no significant difference in overall survival was observed between IBD and non-IBD cohorts (HR 0.89, 95% CI 0.54 to 1.48). Both groups had overall comparable rates of other non-imDC immune-related adverse events.ConclusionPatients with preexisting IBD had worse time-to-imDC than non-IBD matched controls, yet did not exhibit worse overall survival. While close monitoring of patients with preexisting IBD is warranted while on immunotherapy, this comorbidity should not preclude ICI therapy if clinically required.

Review article: Contemporary management of gastrointestinal, pancreatic and hepatic toxicities of immune checkpoint inhibitors

“…14,15 While the presence of preexisting IBD or microscopic colitis is not absolute contraindication to ICI therapy, patient evaluation should include an assessment of disease activity with risk-benefit analysis prior to immunotherapy initiation and close monitoring while on immunotherapy (expert opinion). [14][15][16][17][18][19] ICI colitis presents as loose stools with increased frequency over baseline (diarrhoea), with or without abdominal tenderness on physical examination; more severe cases may also include cramping abdominal pain, urgency, tenderness to abdominal palpation and hematochezia, though the absence of these additional signs/symptoms does not exclude the diagnosis. 20 Fever is also possible though may raise concern for a complication or non-ICI aetiology (e.g.…”

“…Preexisting inflammatory bowel disease (IBD) and microscopic colitis also appear to confer an increased risk of exacerbation and ICI colitis 14,15 . While the presence of preexisting IBD or microscopic colitis is not absolute contraindication to ICI therapy, patient evaluation should include an assessment of disease activity with risk–benefit analysis prior to immunotherapy initiation and close monitoring while on immunotherapy (expert opinion) 14–19 …”

The JAK-STAT Pathway as a Therapeutic Strategy in Cancer Patients with Immune Checkpoint Inhibitor-Induced Colitis: A Narrative Review

“…The primary comorbidity frequently examined is the presence of pre-existing inflammatory bowel disease (IBD). Some evidence suggests that, in patients with IBD, ICI colitis becomes a condition requiring more significant management attention, with a longer duration of the disease [39]. Interestingly, this does not appear to directly impact the oncological response [39].…”

Neoadjuvant immunotherapy in primary and metastatic colorectal cancer

“…Early concern about immunotherapy-induced colitis preventing subsequent surgery seems unwarranted, with very low numbers (< 1–5 per cent) found across 145 trials 77 , of which only three were conducted in patients with CRC. A slightly higher risk may be found in inflammatory bowel disease-associated cancers, but none have been reported to have treatment-limiting effects 78 . Fatal toxic event rates are very low for ICI (between 0.3 and 1.3 per cent), but with the vast majority of data coming from studies in patients with end-stage melanoma or lung cancer 79 .…”