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Chronic Use of Proton Pump Inhibitors Is Associated With an Increased Risk of Immune Checkpoint Inhibitor Colitis in Renal Cell Carcinoma

  • Author Footnotes
    # J.Y. and R.E. contributed equally to this work.
    Jianyi Yin
    Footnotes
    # J.Y. and R.E. contributed equally to this work.
    Affiliations
    Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX
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  • Author Footnotes
    # J.Y. and R.E. contributed equally to this work.
    ,
    Author Footnotes
    † R.E. current address: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 401 N Broadway, Baltimore, MD 21231.
    Roy Elias
    Footnotes
    # J.Y. and R.E. contributed equally to this work.
    † R.E. current address: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 401 N Broadway, Baltimore, MD 21231.
    Affiliations
    Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX

    Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX
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  • Lan Peng
    Affiliations
    Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX
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  • Nicholas Levonyak
    Affiliations
    Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX
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  • Annapoorani Asokan
    Affiliations
    University of Texas Southwestern Medical School, Dallas, TX
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  • Alana Christie
    Affiliations
    Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX
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  • Nisa Kubiliun
    Affiliations
    Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX
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  • James Brugarolas
    Affiliations
    Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX

    Division of Hematology and Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX
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  • Hans J. Hammers
    Correspondence
    Address for correspondence: Hans J. Hammers, M.D., Ph.D., Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, Texas 75235.
    Affiliations
    Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX

    Division of Hematology and Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX
    Search for articles by this author
  • Author Footnotes
    # J.Y. and R.E. contributed equally to this work.
    † R.E. current address: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 401 N Broadway, Baltimore, MD 21231.
Published:February 01, 2022DOI:https://doi.org/10.1016/j.clgc.2022.01.017

      Abstract

      Introduction

      Immune checkpoint inhibitors (ICIs) have become a standard of care in metastatic renal cell carcinoma (mRCC) but are associated with immune-related adverse events (irAEs) including colitis. Growing evidence suggests proton pump inhibitors (PPIs) increase the risk of inflammatory bowel disease (IBD). Given the pathophysiological overlap between IBD and ICI colitis, we sought to evaluate the relationship between PPI use and ICI colitis in mRCC patients.

      Patients and Methods

      We performed a retrospective study of adult patients who received ICI therapy for mRCC between 2015 and 2018 at University of Texas Southwestern Medical Center affiliated hospitals. Clinical characteristics, oncological outcomes, ICI colitis details, and PPI use details were collected by manual chart review. The diagnosis of ICI colitis was made via biopsy when available, or by clinical criteria (symptoms and response to immunosuppressive therapy) when biopsy specimens were unavailable or inconclusive. Univariable and multivariable logistic regression analyses were conducted to assess the potential contribution of PPIs to ICI colitis.

      Results

      A total of 176 patients received ICI therapy for mRCC, of which 16 (9.1%) were diagnosed with ICI colitis. Patients with ICI colitis presented with elevated stool lactoferritin and calprotectin and a wide range of endoscopic and histologic findings. There were no significant differences between patients with and without ICI colitis in age, gender, medical comorbidities, RCC history, and overall survival. However, exposure to ipilimumab and PPI use were more frequently observed in patients with ICI colitis than those without. In univariable and multivariable logistic regression analyses, exposure to ipilimumab and chronic use of PPIs > 8 weeks were significantly associated with ICI colitis.

      Conclusion

      In addition to ipilimumab use, chronic use of PPIs may be associated with ICI colitis in patients with mRCC.

      Keywords

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