A PHASE-II TRIAL OF EXTRACORPOREAL PLASMA IMMUNOADSORPTION OF PATIENTPLASMA 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 progre ssion. 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 an d tumor response in these trials is not clear. Based on these data, a Phase II trial of immunoadsorption over a Staphylococcus aureus protei n A column was initiated for patients with metastatic breast cancer. T he authors sought to correlate clinical response with amount of CIC el uted from the columns after immunoadsorption. Methods. The potential r ole of extracorporeal immunoadsorption was determined using protein A columns in treating patients with advanced breast cancer. An immunoads orbent column composed of protein A was bound covalently to an inert s ilica matrix (PROSORBA [IMRE Corporation, Seattle, WA] column). Patien ts underwent a 3-hour on-line procedure phlebotomizing 2000 ml of whol e blood. Patient plasma was passed over PROSORBA columns to remove imm unoglobulin G (IgG) and IgG-related CIC. The treated plasma then was r eunited 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 wer e 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 ye ars (range, 40-69 years). All patients received prior treatment for St age IV breast cancer. The median number of PROSORBA treatments was 12 (range, 1-15 treatments). No toxicities or major objective responses w ere seen noted the 16 patients. One patient with severe chest wall pai n had a symptomatic response. The remaining patients all had disease p rogression. 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 Staphyloc occus aureus Protein A column had no meaningful antitumor activity in patients with advanced breast cancer. In this cohort of patients, an e levated level of Le(x) CIC was not confirmed in the eluates of the col umn compared with a control group of patients without cancer.