Ulcerative esophagitis associated with combined nivolumab and ipilimumab therapy

Endo, Ruriko; Nakamura, Yoshiyuki; Ishizuki, Shoichiro; Ishitsuka, Yosuke; Watanabe, Rei; Okiyama, Naoko; Ito, Yoshimi; Nagafuchi, Miho; Mizokami, Yuji; Fujisawa, Yasuhiro

doi:10.1111/1346-8138.15421

Cited by 8 publications

(10 citation statements)

References 3 publications

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“…Currently, ICIs are used for advanced cancers, and they often cause irAEs, including gastrointestinal mucositis. ICIs-induced esophagitis is thought to be rare and to our knowledge, 26 previous cases of esophagitis caused by ICIs have been published: 10 cases with nivolumab 2-11) , 4 with nivolumab and ipilimumab [12][13][14][15] , 9 with pembrolizumab 8, [16][17][18][19][20][21][22][23] , 1 with atezolizumab 24) , 1 with avelumab 25) , and 1 with durvalumab 26) . In many of these cases, besides discontinuation of the ICI, administration of corticosteroids was required.…”

Section: Discussionmentioning

confidence: 99%

Pembrolizumab-induced esophagitis dissecans superficialis in a patient with squamous cell lung carcinoma

Hoshi

Hirano

Tsukamoto

et al. 2022

Ann. Cancer Res. Therap.

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Pembrolizumab, a treatment for advanced cancers, can cause immune-related adverse events (irAEs), and among these, esophagitis is rare. We report on an 80-year-old man with squamous cell lung carcinoma who started treatment with pembrolizumab at 200 mg every three weeks. After the first administration, the patient developed odynophagia. Esomeprazole did not improve symptoms, and upper gastrointestinal endoscopy and biopsy revealed esophagitis dissecans superficialis, which was considered as an irAE. Oral prednisolone was started, and odynophagia rapidly improved and the mucosal lesions healed. However, steroid withdrawal was unsuccessful because of repeated relapses. When patients on immune checkpoint inhibitors develop dysphagia, esophagitis should be suspected as an irAE.

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Section: Discussionmentioning

confidence: 99%

Pembrolizumab-induced esophagitis dissecans superficialis in a patient with squamous cell lung carcinoma

Hoshi

Hirano

Tsukamoto

et al. 2022

Ann. Cancer Res. Therap.

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“…Because of this, the presence of multiple white plaques in the esophagus was considered a possible mucosal alteration associated with irAEs. Interestingly, esophageal involvement with irAEs is infrequently reported, but cases of multiple ulcers as typical features of esophageal lesions exist [9][10][11][12][13]. Other endoscopic features of esophageal manifestations of irAEs include distal esophagitis resembling Barrett's esophagus [14], thick mucoid secretions, diffuse mucosal congestion with edema, erythema, mucosal friability [15], and ulcers with desquamative esophagitis in the distal esophagus [16].…”

Section: Discussionmentioning

confidence: 99%

Multiple White Plaques in the Esophagus: A Possible Case of Esophageal Mucosal Alteration Associated With Immune-Related Adverse Events of Immune Checkpoint Inhibitors

Iwamuro¹,

Tanaka²,

Kono³

et al. 2022

Cureus

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We report two cases of multiple white plaques in the esophagus that emerged after the administration of immune checkpoint inhibitors. Both patients developed enterocolitis as immune-related adverse events associated with immune checkpoint inhibitors. Esophagogastroduodenoscopy revealed duodenal involvement and multiple white plaques in the esophagus. A biopsy of the esophagus showed predominant CD3 + lymphocyte infiltration, suggesting that esophageal mucosal alterations were associated with immune-related adverse events. In addition, histopathology showed keratinized stratified squamous epithelium in the first case while increased inflammatory cell infiltration in the intraepithelial and subepithelial layers was observed in the second case. These data suggest a different pathogenesis of the multiple esophageal white plaques between the two cases. Although further investigation is needed to elucidate the significance of these observations, recognition of the esophageal plaques may be important for prompt diagnosis of immune-related adverse events when associated with immune checkpoint inhibitors.

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“…Five case reports described ulcerative esophagitis as a sideeffect after nivolumab, combined treatment with nivolumab and ipilimumab, pembrolizumab or durvalumab therapy. The cases had very different outcomes, two were rapidly improved by corticosteroids [19,20], one developed an esophageal stenosis and responded to tocilizumab treatment [21] and, unfortunately, a patient treated with pembrolizumab died [22]. Another patient treated with pembrolizumab who developed esophagitis had complete resolution of symptomatology after anti-PD-1 therapy cessation [23].…”

Section: Discussionmentioning

confidence: 99%

“…We found five cases of ulcerative esophagitis after nivolumab, pembrolizumab, ipilimumab or durvalumab therapy for different types of cancer [19][20][21][22][23], with patients presenting different outcomes from well-responders to corticosteroids to fatal events. Unusual cases of gastritis were reported, such as steroid refractory [24] or neutrophilic gastritis [25] under nivolumab therapy.…”

Section: Gastrointestinal Tract Toxicitymentioning

confidence: 97%

Digestive Toxicities Secondary to Immune Checkpoint Inhibition Therapy – Reports of Rare Events. A Systematic Review

Radulescu

Crişan

Grapa

et al. 2021

JGLD

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Background and Aims: While immune checkpoint inhibitors therapy (ICI) is exceedingly effective, these drugs are associated with various immune-related adverse effects. As gastrointestinal, hepatic or pancreatic toxicity becomes more common, various reports of rare adverse effects have emerged, leading to a significant clinical and prognostic impact. We aimed to provide a systematic review of mainly case-reports on rare events, to help physicians to make an accurate and fast diagnosis. Methods: We performed a systematic review of the literature, using established MeSH terms: “immune checkpoint inhibitors”, “gastrointestinal tract”, “gastrointestinal diseases”, “liver”, “pancreas”, “nivolumab”, “ipilimumab”, the subheadings “adverse effects”, “toxicity” and the supplementary concepts “pembrolizumab”, “tremelimumab”, “atezolizumab”, “avelumab”, “durvalumab”, with defined inclusion criteria. Results: From 419 manuscripts initially selected, 74 reports of rare adverse events were included in our review. Special cases of neutrophilic gastritis, hemorrhagic gastritis, or even perforations were described at upper digestive tract. Different types of colitis were found secondary to ICI such as pseudomembranous, granulomatous, collagenous and microscopic colitis or even inflammatory bowel disease. In terms of liver toxicity, we found rare reports of cholangitis, granulomatous hepatitis, lipodystrophy and hepatic sinusoidal obstruction syndrome. Pancreas toxicity was rarely reported as severe pancreatitis, exocrine failure and diabetes mellitus. Conclusion: Although a complete check-up of every organ at every routine visit may not be practical, focus on symptoms, targeted laboratory and imaging testing may reveal rare organ damage. Raising awareness of the uncommon toxicities related to the immunotherapy is essential, as some rare events can lead to fatal outcomes.

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Ulcerative esophagitis associated with combined nivolumab and ipilimumab therapy

Cited by 8 publications

References 3 publications

Pembrolizumab-induced esophagitis dissecans superficialis in a patient with squamous cell lung carcinoma

Pembrolizumab-induced esophagitis dissecans superficialis in a patient with squamous cell lung carcinoma

Multiple White Plaques in the Esophagus: A Possible Case of Esophageal Mucosal Alteration Associated With Immune-Related Adverse Events of Immune Checkpoint Inhibitors

Digestive Toxicities Secondary to Immune Checkpoint Inhibition Therapy – Reports of Rare Events. A Systematic Review

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