Mucosal Change like Hypertrophic Gastritis Following Zolbetuximab-Based Therapy in a Conversion Surgery Case of Advanced Gastric Cancer

Background and Clinical Significance: Zolbetuximab, a claudin 18.2 (CLDN18.2)-targeted monoclonal antibody, has shown promise as a therapeutic approach for patients with advanced gastric cancer expressing this target antigen. While established adverse effects include nausea and vomiting, emerging clinical observations have identified hypoalbuminemia as an additional concern that may impact treatment outcomes and surgical planning. Understanding the potential mechanisms of this adverse effect may be important for optimizing patient management and ensuring safe therapeutic interventions. This case report describes a possible relationship between Zolbetuximab-induced mucosal alterations and protein loss, providing valuable insights for clinicians managing patients receiving this targeted therapy. Case Presentation: We present a 53-year-old male patient diagnosed with unresectable advanced gastric cancer who received Zolbetuximab-based combination therapy. The patient demonstrated a favorable therapeutic response, achieving tumor regression that enabled conversion surgery. During treatment, hypoalbuminemia was observed as a notable adverse effect. Histopathological examination of the surgical specimen revealed hypertrophic gastritis with marked foveolar hyperplasia and increased mucus secretion. These findings suggest a possible mechanistic relationship between Zolbetuximab-induced gastric mucosal changes and the development of hypoalbuminemia, potentially through enhanced protein loss via altered gastric mucosa. Conclusions: This case suggests that Zolbetuximab may induce gastric mucosal changes characterized by hypertrophic gastritis and foveolar hyperplasia, which could potentially contribute to hypoalbuminemia development. Clinicians may consider monitoring albumin levels during Zolbetuximab therapy and implementing appropriate nutritional support strategies when indicated. These findings highlight the potential importance of understanding drug-specific adverse effects to optimize patient outcomes and facilitate safe conversion surgery planning in gastric cancer patients receiving targeted therapy.