Immune checkpoint inhibitor-related colitis assessment and prognosis: can IBD scoring point the way?

Abstract

BACKGROUND: Immune checkpoint inhibitors (ICI) improve survival but cause immune-related adverse events (irAE). We sought to determine if CTCAE classification, IBD biomarkers/endoscopic/histological scores correlate with irAE colitis outcomes. METHODS: A dual-centre retrospective study was performed on patients receiving ICI for melanoma, NSCLC or urothelial cancer from 2012 to 2018. Demographics, clinical data, endoscopies (reanalysed using Mayo/Ulcerative Colitis Endoscopic Index of Severity (UCEIS) scores), histology (scored with Nancy Index) and treatment outcomes were analysed. RESULTS: In all, 1074 patients were analysed. Twelve percent (134) developed irAE colitis. Median patient age was 66, 59% were male. CTCAE diarrhoea grade does not correlate with steroid/ infliximab use. G3/4 colitis patients are more likely to need infliximab (p < 0.0001) but colitis grade does not correlate with steroid duration. CRP, albumin and haemoglobin do not correlate with severity. The UCEIS (p = 0.008) and Mayo (p = 0.016) scores correlate with severity/infliximab requirement. Patients with higher Nancy indices (3/4) are more likely to require infliximab (p = 0.03). CONCLUSIONS: CTCAE assessment does not accurately reflect colitis severity and our data do not support its use in isolation, as this may negatively impact timely management. Our data support utilising endoscopic scoring for patients with >grade 1 CTCAE disease, and demonstrate the potential prognostic utility of objective histologic scoring.

Editorial: the microscope holds the key to predict need for biologic therapy in immunotherapy‐checkpoint inhibitory colitis. Authors' reply

“…These findings are consistent with our understanding of the role of histological activity measurements in ulcerative colitis, where outcomes are tightly linked to histological findings 3,4 . The lack of association between clinical measures of ICI colitis and histological findings is also similar to ulcerative colitis and has been seen in other studies of ICI colitis 5 . We used the Robarts Histopathology Index (RHI), a system specifically designed for ulcerative colitis, to measure disease activity.…”

Mucosal-associated invariant T (MAIT) cells are activated in the gastrointestinal tissue of patients with combination ipilimumab and nivolumab therapy-related colitis in a pathology distinct from ulcerative colitis

“…The pathogeneses of ICI toxicities are poorly understood, with few known risk factors, biomarkers [4,39,40] or tailored therapies. As a result, clinicians cannot identify those at greatest risk or intervene to alter therapy before morbidity occurs.…”

“…The augmented adaptive immunity induced by ICI comes at the cost of immune-related adverse events (irAE), most commonly affecting the skin, endocrine organs and gastrointestinal tract. Up to 44% of patients receiving combination anti-CTLA-4 and PD-1 inhibition develop colitis, higher than is seen with anti-PD-1 monotherapy [1,4]. ICI-related colitis typically occurs within the first few treatment cycles (3-9 weeks) as a single-episode illness [5].…”

PD-L1 upregulation is associated with activation of the DNA double-strand break repair pathway in patients with colitic cancer

“…[27] In contrast, enterocolitis is known as one of the most common adverse events associated with ICIs, and it is distinct with clinical and pathological characteristics similar to that of in ammatory bowel disease (IBD). [28,29] A recent study showed patients with pre-existing IBD to be at an increased risk for several gastrointestinal adverse events associated with ICIs, and the safety of ICI treatment for patients with preexisting IBD is undetermined. [30] However, TNF-α blockade treatment in patients with IBD strongly inhibits in ammation in the colorectal mucosa by suppressing several pro-in ammatory pathways, including the TNF-α pathway [31] , and immunosuppressive therapy, including TNF-α blockade and vedolizumab, which is an α4β7 integrin inhibitor blocking the migration of gut-speci c lymphocytes into the gut, is administered for treating not only IBD, but also ICI-induced colitis.…”