Increased doses of an anti-CD30 antibody, MDX-060, results in prolonged progression free survival in subjects with CD30 positive lymphoma.
Abstract Number: 5525
Author Block:
Stephen M. Ansell, Steven Horwitz, Andreas Engert, Khuda Khan, Thomas Lin, Roger Strair, Albert Assad, Michael Yellin, Robert Graziano, Diann Blanset, Jason Tian, Zuoshun Zhang, Claire Barcellona, Peter Borchmann. Mayo Clinic College of Medicine, Rochester, MN, Memorial Sloan Kettering Cancer Center, New York, NY, University Hospital of Cologne, Köln, Germany, Indiana Oncology Hematology Consultants, Indianaplois, IN, Ohio State University Medical Center, Columbus, OH, UMDNJ, New Brunswick, NJ, Medarex, Bloomsbury, NJ
MDX-060 is a human anti-CD30 IgG1kappa monoclonal antibody that inhibits the growth of CD30+ lymphoma cells. To determine the safety and efficacy of MDX-060 in patients with relapsed or refractory CD30+ lymphomas, MDX-060 was administered intravenously at doses of 0.1, 1, 5, 10 or 15 mg/kg weekly for 4 weeks in a phase I/II clinical trial. As previously reported, 72 patients were included in the study - 3 patients received 0.1mg/kg, 16 patients 1mg/kg, 20 patients 5mg/kg, 16 patients 10mg/kg and 17 patients received 15mg/kg. Treatment with MDX-060 was well tolerated with few side effects, however only 6 patients had a clinical response to therapy. Based on the premise that interference with CD30 signaling may result in the arrest of cell growth rather than lysis of the cell, we have now conducted a further analysis with longer follow up to assess whether higher doses of MDX-060 resulted in increased numbers of patients with stable disease and a longer progression free survival (PFS). When patients treated with doses of MDX-060 ³10mg/kg (high dose group: n=33) were compared to patients who received doses of MDX-060 <10mg/kg (low dose group: n=39), both groups had 3 patients who had a response to treatment (1CR and 2 PRs in the low dose group, 3 CRs in the high dose group). However, in the patients in the high dose group 14 patients (42%) had stable disease after treatment compared to 10 patients (26%) in the low dose group. This resulted in a prolonged PFS for patients in the high dose group. Patients in the high dose group had a median PFS of 111days compared to 59 days in the low dose group (p=0.037, Figure 1). At 4 months after treatment with MDX-060, 13 patients (39%) in the high dose group had not had evidence of disease progression compared to 7 patients (18%) in the low dose group. The hazard ratio for disease progression and death of the high dose group compared to the low dose group was 0.58 (95% CI, 0.34 to 0.98, p=0.042). For £1 (0.1 and 1), 5, 10, 15 mg/kg dose groups, the median PFS were 64, 57, 92, 123 days respectively. We therefore conclude that treatment with MDX-060 predominantly results in arrest of CD30+ lymphoma cell growth, and increased doses of the antibody increases the number of patients with stable disease after therapy. The use of higher doses of MDX-060 therefore translates into an increased PFS for patients with CD30+ lymphomas. |
