A Phase II Multicenter Study of Visilizumab, Humanized Anti-CD3 Antibody, to Treat Steroid-Refractory Acute Graft-versus-Host Disease  Paul A. Carpenter, James Lowder, Laura Johnston, Haydar Frangoul, Hanna Khoury, Pablo Parker, Keith R. Jerome, Jeannine S. McCune, Barry Storer, Paul Martin, Frederick Appelbaum, Rafat Abonour, Peter Westervelt, Claudio Anasetti  Biology of Blood and Marrow Transplantation  Volume 11, Issue 6, Pages 465-471 (June 2005) DOI: 10.1016/j.bbmt.2005.03.002 Copyright © 2005 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 1 Kaplan-Meier probability of overall survival after the administration of visilizumab. A, All study participants. B, Survival is shown separately for subjects with serum bilirubin ≥3 mg/dL or with GVHD that was treated with mycophenolate mofetil before enrollment (lower curve; n = 25) and for subjects who had neither of these risk factors (upper curve; n = 19). Survival more than 100 days was observed in 2 of 15 subjects treated with mycophenolate mofetil before enrollment and 2 of 14 subjects with serum bilirubin ≥3 mg/dL. Biology of Blood and Marrow Transplantation 2005 11, 465-471DOI: (10.1016/j.bbmt.2005.03.002) Copyright © 2005 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 2 GVHD response after the administration of visilizumab. Shown are the percentages of patients with complete (solid bars) or partial (stippled bars) responses to visilizumab at weekly time points for all subjects (A), for subjects who had serum bilirubin ≥3 mg/dL or who were being treated with mycophenolate mofetil (B), and for subjects whose serum bilirubin was <3 mg/dL and were not being treated with mycophenolate mofetil (C). The number of patients evaluated for each response is indicated above each bar for each time point. Biology of Blood and Marrow Transplantation 2005 11, 465-471DOI: (10.1016/j.bbmt.2005.03.002) Copyright © 2005 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 3 Visilizumab pharmacokinetics and T-lymphocyte recovery. A, The left panel shows mean ± SEM serum concentrations of visilizumab as measured by a biotinylated streptavidin (SA)–horseradish peroxidase (HRP) assay for 43 evaluable subjects treated with a single dose of 3.0 mg/m2 on the phase II study (♦). Results are from day 1 (within 30 minutes before dosing and 1 and 4 hours after dosing; n = 43), day 2 (24 hours; n = 42), and days 7 (n = 42), 14 (n = 33), 21 (n = 28), 28 (n = 20), 35 (n = 20), and 42 (n = 20). The right panel shows comparable phase I study data as measured by a nonbiotinylated SA-HRP assay (□). [10] B, Before the administration of visilizumab, absolute T-cell counts were 45 to 1956/μL (median, 200/μL). After the administration of visilizumab, absolute T-cell counts increased as serum levels of the antibody decreased. Absolute T-cell counts were 20 to 2209/μL (median, 256/μL) at a median of 21 days (range, 14–90 days) after the administration of visilizumab in 17 subjects who could be evaluated. Biology of Blood and Marrow Transplantation 2005 11, 465-471DOI: (10.1016/j.bbmt.2005.03.002) Copyright © 2005 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 4 Kaplan-Meier probability of survival without Epstein-Barr virus (EBV) reactivation. Shown is the probability of remaining alive after a single 3 mg/m2 dose of visilizumab and without development of plasma EBV DNA levels >1000 copies per milliliter for subjects in the current study (solid line) compared with subjects in the earlier phase I study (stippled line). Biology of Blood and Marrow Transplantation 2005 11, 465-471DOI: (10.1016/j.bbmt.2005.03.002) Copyright © 2005 American Society for Blood and Marrow Transplantation Terms and Conditions