Cancer Immunotherapy with Anti-CTLA-4 Monoclonal Antibodies Induces an Inflammatory Bowel Disease

Marthey, Lysiane; Mateus, Christine; Mussini, Charlotte; Nachury, Maria; Nancey, Stéphane; Grange, Florent; Zallot, Camille; Peyrin–Biroulet, Laurent; Rahier, Jean–François; Beauregard, M. Bourdier de; Mortier, Laurent; Coutzac, Clélia; Soularue, Émilie; Lanoy, Émilie; Kapel, Nathalie; Planchard, David; Chaput, Nathalie; Robert, Caroline; Carbonnel, Franck

doi:10.1093/ecco-jcc/jjv227

Cited by 301 publications

(341 citation statements)

References 35 publications

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“…Other presenting symptoms are abdominal pain, haematochezia, weight loss, fever, and vomiting [1, 7, 13]. Anti-CTLA-4-induced enterocolitis may be associated with mouth ulcers, anal lesions (fistulas, abscesses, fissures), and extra-intestinal manifestations [14]. The clinician should be alert to the possibility of colitis when bloody diarrhoea is present in conjunction with fever, abdominal pain, or mucus in the stool [12].…”

Section: Clinical Featuresmentioning

confidence: 99%

“…The clinician should be alert to the possibility of colitis when bloody diarrhoea is present in conjunction with fever, abdominal pain, or mucus in the stool [12]. Colitis can mimic inflammatory bowel disease (IBD) [14]. Diarrhoea and colitis severity can be graded according to the Common Terminology Criteria for Adverse Events (Table 1) [13].…”

Section: Clinical Featuresmentioning

confidence: 99%

“…The main biological abnormalities in 39 patients with anti-CTLA-4 induced enterocolitis were anaemia, increased serum C-reactive protein, and low serum albumin levels; faecal calprotectin, measured in 8 patients at the time of enterocolitis, was markedly increased [14]. The main differential diagnoses of ICPI-induced enterocolitis are gastrointestinal infections and tumour-related symptoms [1].…”

Section: Diagnosismentioning

confidence: 99%

“…A study of 39 patients with anti-CTLA-4 enterocolitis showed that in 38/39 patients (97%) there was involvement of the rectum and/or sigmoid, extensive colitis was observed in 23/35 patients (66%), and a patchy distribution in 18/33 patients (55%). In patients who underwent ileoscopy, ileitis was found in 20% [14]. The nature of intestinal inflammation caused by ICPIs shares several morphological features with those seen in IBD [5, 14, 16, 20].…”

Section: Diagnosismentioning

confidence: 99%

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Management of Gastrointestinal Toxicity from Immune Checkpoint Inhibitor

Rocha

Sousa

Salgado

et al. 2018

GE Port J Gastroenterol

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Immune checkpoint inhibitors have shown anti-tumour activity in cancers such as melanoma, renal cell carcinoma, non-small-cell lung cancer, urothelial carcinoma, colorectal cancer, and Hodgkin’s lymphoma. Though immune checkpoint inhibitors have revolutionized the treatment and prognosis of some advanced malignancies, they are also associated with a significant risk of immune-related adverse events. These adverse events can occur in any organ system, but gastrointestinal side effects are among the most commonly reported, with manifestations ranging from mild diarrhoea to severe colitis, sharing some features with inflammatory bowel disease. Anticipating a greater use of these drugs in the future, gastroenterologists should expect to be increasingly faced with gastrointestinal immune-related adverse events. Knowledge of these toxicities, as well as effective management algorithms, is essential to enable early diagnosis and treatment, decreasing morbidity and mortality. We reviewed the currently available literature on gastrointestinal toxicity induced by immune checkpoint inhibitors, namely the clinical features, diagnosis, and management.

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Section: Clinical Featuresmentioning

confidence: 99%

Section: Clinical Featuresmentioning

confidence: 99%

Section: Diagnosismentioning

confidence: 99%

Section: Diagnosismentioning

confidence: 99%

See 2 more Smart Citations

Management of Gastrointestinal Toxicity from Immune Checkpoint Inhibitor

Rocha

Sousa

Salgado

et al. 2018

GE Port J Gastroenterol

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“…Additionally, these studies suggested that two species from the Bacteroidales and Burkholderiales order significantly reduced the histopathological signs of colitis, 3 a common, high-risk, immune-related adverse event associated with anti-CTLA-4 Ab therapy. 4-7 While there is supportive evidence that species from the Bacteroidales order are associated with decreased incidence of colitis in patients administered anti-CTLA-4 Ab, 8 there is also data correlating the colonization of certain Bacteroidales species in the gut with colitis 9 , 10 and Crohn's disease. 11 , 12 Inconsistencies and multiple variables in comparative research force the analysis of factors which might confound the results in this publication, including the possibility of antibiotic resistance and inexplicit microbial baseline values in antibiotic-treated mice models.…”

mentioning

confidence: 99%

The gut microbiota and immune checkpoint inhibitors

Humphries

Daud

2018

Human Vaccines & Immunotherapeutics

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Although immunotherapy has been remarkably effective across multiple cancer types, there continues to be a significant number of non-responding patients. A possible factor proposed to influence the efficacy of immunotherapies is the gut microbiome. We discuss the results and implications of recent research on the relationship between the gut microbiome, our immune systems, and immune checkpoint inhibitor therapies including anti-CTLA-4 Ab and anti-PD-1 Ab. While the investigations all exhibit interesting results and conclusions, we find little congruence in the specific bacteria that were found favorable for antitumor responses. It is unclear whether the inconsistencies are due to differential approaches in study design (pre-clinical or clinical subjects, anti-CTLA-4 Ab or anti-PD-1 Ab), experimental methods and measurements (metagenomics sequencing and clustering variations) or subject population dynamics (differential cancer types and baseline characteristics). Moreover, we note studies regarding particular bacterial commensals and autoimmune diseases, which challenge findings from these investigations. We conclude that with the current research, clinical investigators can appreciate the critical role of gut microbiota in mediating immunostimulant response. However, prospective research exploring the biochemical mechanisms which commensal bacteria communicate with each other and the immune system is imperative to understand how they can be adjusted properly for higher immunotherapy response.

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