Clinicopathologic Features, Treatment Response, and Outcomes of Immune Checkpoint Inhibitor–Related Esophagitis

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  • 1 Department of Internal Medicine, Baylor College of Medicine, Houston, Texas;
  • | 2 Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, Texas; and
  • | 3 Department of Pathology,
  • | 4 Department of Gastroenterology, Hepatology, and Nutrition, and
  • | 5 Department of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas; and
  • | 6 Department of Medicine, University of Washington, Fred Hutchinson Cancer Research Center, Seattle, Washington.
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Background: Although immune checkpoint inhibitors (ICIs) have provided practice-changing outcomes in treating many cancers, ICI-related gastrointestinal toxicity can limit their use. Upper gastrointestinal toxicity is not common nor as well described as lower gastrointestinal toxicity. We aimed to characterize the clinical presentation, endoscopic and histologic features, treatment response, and outcomes of ICI-related esophagitis. Methods: We retrospectively studied patients at The University of Texas MD Anderson Cancer Center in whom esophagitis developed after receiving ICIs from June 2011 through January 2020. We included patients with endoscopic evidence of esophagitis and excluded those with other obvious causes of esophagitis. A chi-square test was used to assess associations between categorical variables. The Mann-Whitney U test was used to compare differences between continuous variables. Results: Of 657 consecutive patients who underwent esophagogastroduodenoscopy (EGD) during or within 6 months of completing ICI-based therapy, 21 (3%) had esophagitis deemed to be from ICIs. Of these patients, 1 (5%) received an inhibitor of CTLA-4 alone, 15 (71%) received anti–PD-1 or PD-L1 monotherapy, and 5 (24%) received a combination of these. Median time from ICI initiation to onset of esophagitis was 4 months. Upon evaluation with EGD, only 3 patients (14%) had isolated esophageal involvement; 18 (86%) had concurrent involvement of the stomach, duodenum, or both. Most patients (67%) were treated with proton pump inhibitors, and 4 (19%) received steroids (prednisone or budesonide). The mortality rate was 38% (median follow-up, 15 months). Conclusions: Esophagitis associated with ICI use is rare. The diagnosis is one of exclusion because its clinical presentation appears similar to that of inflammation resulting from other causes. It often occurs in conjunction with other upper gastrointestinal toxicity. Symptoms are mild and respond well to nonimmunosuppressive treatment, with few severe complications.

Submitted September 5, 2020; final revision received October 18, 2020; accepted for publication October 20, 2020. Published online June 11, 2021.

Author contributions: Study concept and design: Thomas, Wang. Data acquisition: Panneerselvan, Lum. Data analysis and interpretation: Panneerselvan, Thomas, Wang. Manuscript preparation: Panneerselvam, Thomas, Wang. Critical revision: Amin, Zhang, Richards, Altan, Grivas, Thompson, Thomas, Wang. Pathology slide review and histologic images: Wei, Tan.

Disclosures: Dr. Grivas has disclosed serving as a consultant or in an advisory role for AstraZeneca, Bayer, Bristol Myers Squibb, Clovis Oncology, Dyania Health, Driver, EMD Serono, Exelixis, Foundation Medicine, Genentech/Roche, Genzyme, GlaxoSmithKline, Heron Therapeutics, Immunomedics, Infinity Pharmaceuticals, Janssen, Merck & Co., Mirati Therapeutics, Pfizer, QED Therapeutics, and Seattle Genetics; and receiving research support from Bavarian Nordic, Bristol Myers Squibb, Clovis Oncology, Debiopharm, GlaxoSmithKline, Immunomedics, Kure It Cancer Research, Merck & Co., Mirati Therapeutics, Pfizer, and QED Therapeutics. Dr. Thompson has disclosed receiving grant/research support from Merck, Hoffmann-LaRoche, Pfizer, Five Prime, Novartis, Incyte, Trillium, and Xencor; and serving as a consultant for Neoleukin, Aveo, and Regeneron. Dr. Wang has disclosed serving as a consultant for Tillotts Pharma. The remaining authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Correspondence: Yinghong Wang, MD, PhD, Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Unit 1466, 1515 Holcombe Boulevard, Houston, TX 77030. Email: ywang59@mdanderson.org
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