Intraperitoneal nivolumab for malignant ascites in patients with advanced gastrointestinal or pancreaticobiliary...

Malignant ascites occur in 10-15% of patients with gastrointestinal tract cancers. The abundance of immune cells in the peritoneum and ascitic fluid, along with the immunosuppressive environment created by cancer cells, suggests the potential utility of intraperitoneal (IP) immune checkpoint inhibitors for controlling malignant ascites.

Patients with gastrointestinal or pancreaticobiliary tract cancer and cytologically confirmed malignant ascites received IP nivolumab. Twenty mg of nivolumab diluted in 100 mL of saline was infused into the peritoneal cavity over 10 min following paracentesis. IP treatment was repeated after each subsequent paracentesis until deemed ineffective by the treating physician, upon the occurrence of unacceptable toxicity, or discontinued at the patient's request. This study was registered at ClinicalTrials.gov (NCT05745233).

The median age of the nine enrolled patients was 55 years. Underlying malignancies included pancreatic (n = 4), biliary tract (n = 3), and gastric cancers (n = 2). After a median of 3 (range: 2-5) treatment cycles, seven patients (77.8%) showed a clinical response, as evidenced by reduced ascitic fluid and prolonged intervals between paracenteses. The only adverse effect observed was grade 1 tenderness at the puncture sites. Reduction in tumor cell count in ascites, rather than changes in the total lymphocyte count or lymphocyte subpopulations, correlated with clinical response. Responders consistently exhibited increased vascular endothelial growth factor A and decreased interleukin-1α levels following nivolumab administration.

Intraperitoneal administration of nivolumab effectively controlled malignant ascites with minimal adverse effects. However, further validation in a larger cohort is required.