Increased risk of gastrointestinal complications in older adults with multiple myeloma: A propensity matched nationwide cohort study

Abstract Background: Multiple myeloma (MM) is a plasma cell malignancy predominantly affecting older adults. Although therapeutic advancements have extended survival, the incidence and burden of gastrointestinal (GI) complications in this population is not well defined. Given the frequent use of GI toxic therapies and the proinflammatory, immunosuppressive milieu associated with MM, older patients may be at increased risk for upper GI disorders. This study aimed to evaluate the incidence of GI complications in individuals aged ≥60 years with MM compared to matched non-MM controls, and to assess the additional risk conferred by Stem Cell Transplant (SCT) within the MM cohort. Methods: A retrospective cohort analysis was conducted using the TriNetX US Collaborative Network. Adults aged ≥60 with MM and no prior GI disorders were compared with non-MM controls who had atleast one visit to the hospital, from 2015-2020. The groups were propensity matched 1:1 based on demographics, cirrhosis status, BMI, and use of non-salicylate NSAIDs, PPIs, and H2 blockers. Each cohort included 25,992 individuals. In the secondary analysis, MM patients who underwent SCT were matched 1:1 to MM patients who did not receive SCT (n=4977). Outcomes included GI complications including hematemesis, melena, esophagitis, gastroesophageal reflux disease (GERD), gastric and duodenal ulcers, peptic ulcer, functional dyspepsia, and gastric intestinal metaplasia. Risk and time-to-event analyses were performed excluding patients with preexisting outcomes. Results: Compared to controls, MM patients exhibited significantly higher odds of hematemesis (OR 7.32, 95% CI 3.78–14.18), melena (OR 8.41, 95% CI 5.92–11.95), esophagitis (OR 5.53, 95% CI 3.70–8.27), and GERD (OR 3.95, 95% CI 3.56–4.38). Similarly, the risk of gastric ulcer (OR 5.96, 95% CI 3.51–10.13), duodenal ulcer (OR 4.01, 95% CI 2.00–8.01), peptic ulcer (OR 4.51, 95% CI 2.27–8.95), and functional dyspepsia (OR 6.21, 95% CI 3.19–12.12) was markedly elevated in the MM group. Kaplan-Meier analyses demonstrated significantly reduced GI event-free survival among MM patients across all outcomes (log-rank p<0.001). In the SCT subgroup analysis, SCT recipients had higher odds of melena (OR 1.37, 1.02-1.54), esophagitis (OR 1.76, 1.19-2.60), GERD (or1.36, 1.20-1.54), and functional dyspepsia (OR 2.01, 1.12-3.60) compared to non-MM cohorts. No statistically significant differences were observed in hematemesis, gastric ulcer, duodenal ulcer or peptic ulcer. Kaplan-Meier curves showed a trend towards reduced GI event free survival in SCT patients. Conclusion: Older adults with multiple myeloma are at substantially increased risk for a broad spectrum of upper gastrointestinal complications compared to non-MM counterparts. Additionally, SCT increases the risk of reflux related disorders and functional dyspepsia among patients with MM. These findings highlight the importance of proactive GI risk assessment and implementation of gastroprotective strategies in the comprehensive care of MM patients.