Association of chronic use of proton pump inhibitors with an increased risk of immune checkpoint inhibitor-induced colitis in renal cell carcinoma.

Abstract

e16550 Background: Immune checkpoint inhibitors (ICI) have become standard of care in metastatic renal cell carcinoma (mRCC) but are associated with immune-related adverse events (irAEs) including immune-related colitis (irC). Growing evidence suggests that proton pump inhibitors (PPIs) are associated with an increased risk of inflammatory bowel disease (IBD). Given the pathophysiological overlap between IBD and irC, we sought to evaluate the relationship between PPI use and irC in mRCC patients. Methods: We performed a retrospective study of adult patients who received ICI for mRCC between 2015 and 2018 at two tertiary care centers. Clinical characteristics, oncological outcomes, irC details, and PPI use were collected by manual chart review. The diagnosis of irC was made via biopsy when available, or when unavailable (or inconclusive) by clinical criteria. Univariable and multivariable logistic regression analyses were conducted to assess PPI use and other potential risk factors of irC. Results: A total of 176 patients received immunotherapy for mRCC, of which 16 (9.1%) were diagnosed with irC. There were no significant differences between patients with and without irC in age, gender, medical comorbidities, RCC subtype, treatment history, and overall survival. However, Caucasian race, exposure to ipilimumab, and PPI use were more frequently observed in patients with irC than those without. Patients with irC presented with elevated stool lactoferrin and calprotectin and a wide range of endoscopic and histologic findings. In univariable and multivariable logistic regression analyses, Caucasian race, exposure to ipilimumab and chronic use of PPIs >8 weeks were significantly associated with irC (Table). Conclusions: PPI use may be a modifiable risk factor for irC development in patients with mRCC.[Table: see text]