Removal of EpCAM-positive tumor cells during intraoperative blood salvage- A pivotal multicenter clinical study (REMOVE).

BACKGROUND: Intraoperative blood salvage can reduce the need for allogeneic blood transfusions, minimizing immunological risks and infection by reusing the patient's own blood. However, in cancer surgery, a key concern limiting its use is the potential reintroduction of viable cancer cells. Additional risks, such as infection and coagulopathy, have also contributed to its limited adoption. Irradiation of salvaged blood remains an option; however, it is time-intensive and may have detrimental effects on blood cells. These challenges highlight the need for improved technologies to enable safe application in oncological procedures. One such promising tool is CATUVAB®, which removes epithelial cell adhesion molecule (EpCAM)-positive tumor cells from salvaged blood.

METHODS: In this multicenter, clinical validation study, patients undergoing major surgery for bladder cancer, gastric carcinoma, ovarian carcinoma, pancreatic carcinoma, colon/rectal carcinoma, non-small cell lung cancer, or peritoneal carcinomatosis were included. The primary objective of the study was to elucidate the efficacy of CATUVAB® in depleting intraoperatively salvaged blood of EpCAM-positive tumor cells. Secondary objectives included the determination of residual Catumaxomab antibody amount and cytokine levels in the final erythrocyte concentrate (EC).

RESULTS: 203 patients were assessed for eligibility, and 80 were included in the safety analysis, of whom 61 had EpCAM-positive tumor cells in intraoperative blood. The primary efficacy analysis demonstrated a 100 % (95 % CI (95.8 %-100 %)) rate of sufficient depletion of EpCAM-positive tumor cells (p < 0.0001). In 117 out of 131 EC samples (89 %) the catumaxomab concentration was below the limit of quantification. Additionally, cytokines IL-6 and IL-8, typically due to surgical trauma, were significantly reduced (30- to 38-fold) in ECs compared to intraoperative blood.

CONCLUSION: The study demonstrates the efficacy, safety and feasibility of CATUVAB® for the re-infusion of autologous EC processed by a cell salvage device during high-blood-loss cancer surgeries. These promising results have the potential to re-define the intraoperative blood salvage protocols in cancer surgeries.