Ipilimumab and immune-mediated adverse events: a case report of anti-CTLA4 induced ileitis

Venditti, Olga; Lisi, Delia De; Caricato, Marco; Caputo, Damiano; Capolupo, Gabriella Teresa; Taffon, Chiara; Pagliara, E.; Battisi, Sofia; Frezza, Anna Maria; Muda, Andrea Onetti; Tonini, Giuseppe; Santini, Daniele

doi:10.1186/s12885-015-1074-7

Cited by 34 publications

(16 citation statements)

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“…To our knowledge, only one case of ipilimumab-induced ileitis without colitis that resulted in ileal perforation has been reported in the literature 4. The authors hypothesise that there could be two different pathways activated against colic and ileal epitopes resulting in two distinguished pattern of gastrointestinal involvement.…”

Section: Descriptionmentioning

confidence: 98%

Severe inflammatory ileitis resulting in ileal perforation in association with combination immune checkpoint blockade for metastatic malignant melanoma

Mohamed¹,

Richards

Boyle

et al. 2018

BMJ Case Reports

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SummaryImmune checkpoint inhibitors have become standard of care in metastatic malignant melanoma management. Despite superior effectiveness to chemotherapy, significant immune-related adverse events (irAE) may occur, particularly if used in combination. Gastrointestinal irAEs were reported with different patterns of involvement. Here, we report the case of a patient who had ileal perforation as a complication of terminal ileitis, without colitis, induced by combination immune checkpoint blockade. DeSCripTionImmune checkpoint inhibitors have become standard of care in metastatic malignant melanoma management. Despite superior effectiveness to chemotherapy, significant immune-related adverse events (irAE) may occur, particularly if used in combination.

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Section: Descriptionmentioning

confidence: 98%

Severe inflammatory ileitis resulting in ileal perforation in association with combination immune checkpoint blockade for metastatic malignant melanoma

Mohamed¹,

Richards

Boyle

et al. 2018

BMJ Case Reports

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“…Of the 1892 unique studies identified using our search criteria, 61 studies fulfilled our inclusion criteria and were included in the qualitative analysis (38 full text articles, 23 in abstract form) . Results of our search strategy are depicted in Figure .…”

Section: Resultsmentioning

confidence: 99%

“…While not a primary study outcome, we identified four reports describing five patients with checkpoint inhibitor‐induced isolated upper gastrointestinal tract inflammation . All patients reported symptomatic diarrhoea; one patient with oesophageal involvement also reported dysphagia.…”

Section: Resultsmentioning

confidence: 99%

Systematic review and case series: flexible sigmoidoscopy identifies most cases of checkpoint inhibitor‐induced colitis

Wright

Piper

Bishu

et al. 2019

Aliment Pharmacol Ther

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Summary Background Immune checkpoint inhibitors are used in the treatment of multiple advanced stage cancers but can induce immune‐mediated colitis necessitating treatment with immunosuppressive medications. Diagnostic colonoscopy is often performed but requires bowel preparation and may delay diagnosis and treatment. Sigmoidoscopy can be performed rapidly without oral bowel preparation or sedation. Aims Characterize the colonic distribution of immune‐mediated colitis to determine the most efficient endoscopic approach. Methods A systematic review of checkpoint inhibitor‐induced colitis case reports and series was conducted in both PubMed and Embase through 3 January 2017. A single centre retrospective chart review of patients who underwent endoscopic evaluation for diarrhoea after treatment with a checkpoint inhibitor (ipilimumab, nivolumab or pembrolizumab) between 1 January 2011 and 3 January 2017 was performed. Clinical, endoscopic and histologic data were collected. Results A detailed systematic review resulted in 61 studies, in which 226 cases of colitis were diagnosed by lower endoscopy (125 colonoscopy, 101 sigmoidoscopy). Only four patients had isolated findings proximal to the left colon. In our centre, 31 patients had histologic features of checkpoint inhibitor‐induced colitis, for which 29 patients had complete data. The left colon was involved in all cases. Sigmoidoscopy would be sufficient to diagnose >98% of reported cases of checkpoint inhibitor‐mediated colitis diagnosed by lower endoscopy. Conclusions Moderate to severe checkpoint inhibitor‐induced colitis involves the left colon in the majority of cases (>98%). Sigmoidoscopy should be the initial endoscopic procedure in the evaluation of this condition.

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“…While diarrhoea is defined by the increase in frequency or change in the consistency of stool, colitis is often in this clinical scenario defined by the presence of abdominal pain or tenderness, presence of blood in stool or radiological evidence of large bowel inflammation. Inflammation of the small bowel is uncommon but has been reported with the use of ipilimumab [24]. Mortality has been reported in 1% of cases i.e.…”

Section: Gastrointestinal Toxicitymentioning

confidence: 99%

“…In clinically suspected hypophysitis, the pituitary axis should be evaluated, namely the morning cortisol, the ACTH, TSH, LH, FSH, prolactin, testosterone in men and oestradiol in women [7]. MRI pituitary may contribute to the diagnostic process with the main findings being pituitary enlargement, abnormal enhancement or atrophy [10,24]. However, normal findings can also be seen when the MRI imaging is taken after the initiation of high dose corticosteroids [7].…”

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confidence: 99%

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2016

JCPCR

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Background: Over the last 5 years ever since Ipilimumab received FDA approval for the treatment of metastatic melanoma, immunotherapy as a treatment modality is making its presence felt in oncology clinics across the globe. While initially approved for the treatment of metastatic melanoma alone, the immunotherapy repertoire is ever expanding with its' utility being assessed for in the metastatic and adjuvant setting. The adverse effect profile from immunotherapy drugs differs from that of conventional chemotherapy that oncological services have trained in managing over the last few decades. This raises the need for educating health care professionals as the scenarios that patients present with at acute admissions or in clinic secondary to immune related adverse effects (iRAEs) can often be misleading. Aims:This review aims to synopsise the common and less common iRAEs and highlight their varied presentations, in addition to stressing the need to institute timely immunosuppression, which forms the cornerstone in the management of iRAEs.Recommendations: iRAEs have been recognised more frequently and in greater severity in dose dense and combination treatment regimens. While dermatological, gastrointestinal, hepatic toxicities in addition to endocrinopathies are the most commonly encountered iRAEs though other organ systems can be involved. The appropriate grading of an iRAEs' severity, delaying or discontinuing immunotherapy based treatment, supportive care, commencement of immunosuppression (with corticosteroids and/or steroid sparing agents) and a multidisciplinary approach are key constituents in the treatment pathway of iRAEs. Conclusion:Early recognition of iRAEs and timely commencement of appropriate immunosuppression is imperative in order to reduce the risk of significant morbidity and potential mortality. The management of iRAEs warrants a multidisciplinary approach which would be aided by the development of local guidelines and educational activities directed at providing health care professionals with the information and tools required to recognise and appropriately treat iRAEs. IntroductionOver the last few decades there has been an increasing interest in the field of cancer immunotherapy. The manipulation of the immune system using immunotherapeutic interventions has changed the therapeutic landscape in many type of cancers [1][2][3][4]. However, immunotherapy carries immune-related adverse effects (irAEs) which can be significant [5][6][7]. irAEs are usually reversible but occasionally can be life-threatening [5][6][7]. A retrospective study on the irAEs of Ipilimumab showed that 85% of patients experienced irAEs of any grade of whom 19% discontinued therapy [8]. 35% patients required systemic corticosteroids and 10% required anti-TNF therapy for irAEs [8]. There were no significant differences in overall survival in those with and without irAEs or between those who received corticosteroids or not [8,9]. Hence, this requires the development of treatment protocols and training of the healthcar...

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Ipilimumab and immune-mediated adverse events: a case report of anti-CTLA4 induced ileitis

Cited by 34 publications

References 10 publications

Severe inflammatory ileitis resulting in ileal perforation in association with combination immune checkpoint blockade for metastatic malignant melanoma

Severe inflammatory ileitis resulting in ileal perforation in association with combination immune checkpoint blockade for metastatic malignant melanoma

Systematic review and case series: flexible sigmoidoscopy identifies most cases of checkpoint inhibitor‐induced colitis

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