Transient human anti-mouse antibodies (HAMA) interference in CA 125 measurements during monitoring of ovarian cancer patients treated with murine monoclonal antibody

Objective. To investigate the influence of human anti-mouse antibodies (HAMA) on serial CA 125 measurements in serum of patients with epithelial ovarian cancer following single intraperitoneal (IP) therapy with Yttrium-90-labeled human milk fat globule 1 murine monoclonal antibody (Y-90-muHMFG1) as part of a large international randomized phase III trial. Methods. We monitored CA 125 concentrations in longitudinally collected serum samples from 224 patients after IP Y-90-muHMFG1 (study group) and from 223 patients who received standard treatment (control group). Serum samples of 22 study patients with increased CA 125 concentrations were selected and subjected to affinity chromatography to study HAMA interference in CA 125 measurements. Results. CA 125 serum concentrations at weeks 1, 4 and 8 were significantly higher in the study group than in the control group. In the first 8 weeks after IP Y-90-muHMFG1 administration significantly more patients of the study group (144/224) demonstrated CA 125 concentrations above the upper limit of normal of 23 U/mL, as compared to those of the control group (37/223). Affinity chromatography of serum with high CA 125 values in the first 8 weeks confirmed HAMA interference in CA 125 measurements while after 24 weeks this HAMA interference could no longer be detected. Conclusions. This is the first study to demonstrate that clinical trials applying murine monoclonal antibodies may be flawed by a transient HAMA effect, which should be considered when monitoring ovarian cancer patients with CA 125 measurements. (c) 2008 Elsevier Inc. All rights reserved.