S1713 Proteasome Inhibitors and Colitis: A Comparative Look at Gastrointestinal Complications in Lymphoid and Hematopoietic Malignancies

Introduction: Gastrointestinal complications, particularly various forms of colitis, are a major concern in patients with lymphoid and hematopoietic malignancies. Proteasome inhibitors are increasingly utilized in treatment, but their impact on specific colitis-related conditions, such as cytomegalovirus (CMV) colitis, Ischemic colitis, diverticulitis, remains underexplored. Given the potential severity of these complications, it is crucial to assess whether proteasome inhibitors increase the risk of colitis and other GI disorders in this vulnerable population. This study aims to provide a comparative analysis of colitis-related complications in patients treated with proteasome inhibitors to inform therapeutic decisions and patient management. Methods: We conducted a retrospective cohort analysis using data from 32,589 patients with malignant lymphoid and hematopoietic neoplasms from the TriNetX research network. Two cohorts were identified: patients treated with proteasome inhibitors (Cohort 1) and those without (Cohort 2). Inclusion criteria were age ≥18 years, and patients with a diagnosis of ulcerative colitis or Crohn’s disease were excluded. Propensity score matching was performed to adjust for confounding variables, including age, sex, race, and comorbidities such as type 2 diabetes mellitus, essential hypertension, overweight/obesity, cerebrovascular disease, ischemic heart disease, chronic kidney disease, nicotine dependence, and alcohol abuse. Primary outcomes included colitis-related complications, such as microscopic colitis, CMV colitis, diverticulitis, and ischemic colitis. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox proportional hazards regression. Results: Proteasome inhibitor use was associated with increased risk of CMV colitis (HR 1.595, 95% CI 1.406–1.808), diverticulitis (HR 1.325, 95% CI 1.152–1.524), and ischemic colitis (HR 1.674, 95% CI 0.817–3.432), though the latter was not statistically significant. Microscopic colitis showed a lower, non-significant risk (HR 0.95, 95% CI 0.597–1.518). Conclusion: Proteasome inhibitor use in patients with lymphoid and hematopoietic malignancies was associated with a significantly higher risk of CMV colitis and diverticulitis, as well as an elevated risk of ischemic colitis. In contrast, the risk of microscopic colitis appeared lower. These findings suggest a potential for serious gastrointestinal complications, emphasizing the need for monitoring and a careful approach to proteasome inhibitor therapy.