A phase II trial of extracorporeal plasma immunoadsorption of patient plasma with prosorba columns for treating metastatic breast cancer

BACKGROUND: Circulating immune complexes (CIC) have been implicated as a cause of malignancy-associated immunosuppression and disease progression. Previous attempts to remove CIC by pheresis or immunoadsorption over a Staphylococcus aureus protein A column have resulted in a few clinical responses, however the relationship between removal of CIC and tumor response in these trials is not clear. Based on these data, a Phase II trial of immunoadsorption over a Staphylococcus aureus protein A column was initiated for patients with metastatic breast cancer. The authors sought to correlate clinical response with amount of CIC eluted from the columns after immunoadsorption. METHODS: The potential role of extracorporeal immunoadsorption was determined using protein A columns in treating patients with advanced breast cancer. An immunoadsorbent column composed of protein A was bound covalently to an inert silica matrix (PROSORBA IMRE Corporation, Seattle, WA column). Patients underwent a 3-hour on-line procedure phlebotomizing 2000 ml of whole blood. Patient plasma was passed over PROSORBA columns to remove immunoglobulin G (IgG) and IgG-related CIC. The treated plasma then was reunited with formed elements and reinfused into the patient. Patients were treated three times per week for a total of 4 weeks. Analyses of tumor-associated Le(x)-containing CIC adsorbed on PROSORBA columns were performed using an enzyme-linked immunosorbent assay technique with a monoclonal antibody specific for the Le(x) moiety. RESULTS: Sixteen patients were entered in this Phase II study, with a mean age of 57 years (range, 40-69 years). All patients received prior treatment for Stage IV breast cancer. The median number of PROSORBA treatments was 12 (range, 1-15 treatments). No toxicities or major objective responses were seen noted the 16 patients. One patient with severe chest wall pain had a symptomatic response. The remaining patients all had disease progression. Analyses of column eluates from 11 patients in this study revealed no detectable Le(x)-containing immune complexes when compared with control subjects. CONCLUSIONS: Immunoadsorption over a Staphylococcus aureus Protein A column had no meaningful antitumor activity in patients with advanced breast cancer. In this cohort of patients, an elevated level of Le(x) CIC was not confirmed in the eluates of the column compared with a control group of patients without cancer.