Zolbetuximab-induced Gastric Mucosal Injury and Hypoalbuminemia: A Mechanism-informed Clinical Analysis

Purpose Zolbetuximab plus chemotherapy is standard first-line therapy for HER2-negative, CLDN18.2-positive advanced gastric or gastroesophageal junction cancer (GC/GEJC), but the incidence, course, and clinical correlations of zolbetuximab-related gastric mucosal injury and hypoalbuminemia remain unclear. We thus evaluated these relationships and the clinical course in real-world practice. Methods We retrospectively analyzed 38 patients with HER2-negative, CLDN18.2-positive, advanced GC/GEJC treated with zolbetuximab plus chemotherapy at a single center. Associations between endoscopic findings and albumin changes from baseline were analyzed. Results Median albumin decreased from 3.7 to 2.6 g/dL. The median albumin decline was greater in patients without gastrectomy (− 1.0 g/dL) or with partial gastrectomy (− 1.1 g/dL) than in those with total gastrectomy (− 0.3 g/dL; P = 0.009 and 0.007). Albumin levels fell rapidly at weeks 1–3 and recovered toward baseline by weeks 19–27. Upper gastrointestinal endoscopies were performed in patients with a remaining stomach, showing peak abnormalities within 7–12 weeks; no cases with grade ≥ 2 gastric mucosal injury were observed after week 25. White exudate was associated with albumin decline (− 0.9 vs. −0.4 g/dL, P = 0.023). Conclusions The presence of white exudate demonstrated a significant association with a marked decrease in serum albumin levels. The risk of hypoalbuminemia appeared to be lower in patients after total gastrectomy. Both the decline in serum albumin levels and the gastric mucosal injury appeared to be transient, showing a tendency to improve over time.