Early hypoalbuminemia during zolbetuximab therapy in gastroesophageal adenocarcinoma: a retrospective observational study.

BACKGROUND

Zolbetuximab has improved survival in claudin 18.2 (CLDN18.2)-positive gastroesophageal adenocarcinoma (GEA). Hypoalbuminemia was reported in phase III trials. However, the timing, magnitude, and clinical phenotype of serum protein decline remain incompletely characterized. This study aimed to characterize changes in serum albumin and total protein during zolbetuximab therapy and their associated clinical findings.

METHODS

We performed a retrospective cohort study of patients with CLDN18.2-positive GEA treated with zolbetuximab at Mayo Clinic sites. The primary endpoint was percent change in serum albumin from baseline to the first post-treatment measurement following therapy initiation. Secondary endpoints included percent change in total protein, development of new edema or ascites not attributable to disease progression, and changes in albumin and total protein after treatment discontinuation.

RESULTS

Twenty-four patients were included. Serum albumin declined in all patients, and total protein declined in 23/24 (95.8%) immediately following treatment initiation. After the first cycle, median albumin decreased by 0.9 g/dL (22.5%), and total protein decreased by 1.5 g/dL (23.7%) from baseline. Ten patients (41.7%) developed new edema and 6 (25%) developed ascites, with 8 (33.3%) requiring diuretics and/or paracentesis, without radiographic disease progression. Renal and hepatic laboratory parameters remained stable, and urinalysis did not demonstrate nephrotic-range (grade 3+) proteinuria.

CONCLUSIONS

Zolbetuximab therapy is associated with an early decline in serum albumin and total protein in real-world practice, frequently accompanied by edema or ascites and not explained by renal, hepatic, or progressive disease factors. These findings may reflect a treatment-related gastrointestinal protein-losing process and support close laboratory monitoring and supportive management during therapy. Further studies are warranted to clarify mechanism and clinical impact.