Sipuleucel-T is an autologous cellular immunotherapy for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer. Sipuleucel-T consists of autologous peripheral blood mononuclear cells (PBMCs), including antigen presenting cells (APCs), that have been activated with a recombinant human protein, PAP-GM-CSF (prostatic acid phosphatase [PAP] linked to granulocyte-macrophage colony-stimulating factor [GM-CSF]). It is prepared from cells collected by leukaphereses at Weeks 0, 2, and 4 and infused approximately 3 days following each leukapheresis. In the IMPACT study, 512 patients were randomized (2:1) to sipuleucel-T or control (non-activated autologous PBMCs). Serum samples were collected at Baseline and Weeks 6, 14, and 26, and were analyzed for routine clinical chemistry tests in a comprehensive metabolic panel, which included total protein and albumin. In selected samples, serum protein electrophoresis (SPEP) and densitometry were performed using the Sebia automated electrophoresis system. We observed elevated total protein at Weeks 6 and 14 in sipuleucel-T patients only. At Week 6, 10.0% (28/279) of sipuleucel-T patients with a normal baseline total protein concentration had an elevated total protein concentration (upper limit of normal [ULN] = 7.9 to 8.5 g/dL, depending on age) compared with 0% (0/140) of control patients. At Week 14, 10.4% (19/183) of sipuleucel-T patients with a normal baseline total protein had an elevated total protein compared with 0% (0/86) of control patients. Albumin levels were not elevated at Week 6 following treatment (0.4% ½84 of sipuleucel-T patients with a normal baseline albumin concentration had increases in post-treatment serum albumin), indicating that the changes in total protein were due to elevations in serum globulin. In sipuleucel-T patients, there was a positive correlation between the maximum globulin protein elevations (total protein minus albumin) and the magnitude of antibody titers to PAP-GM-CSF at Week 6 (n = 126; P = 0.001) and Week 14 (n = 85; P = 0.002). Samples from sipuleucel-T patients for whom both a baseline and post-treatment sample were available and who fell within the upper 10th percentile of the total protein change (n = 13) were evaluated by SPEP. All of these patients had increased gamma globulin compared with baseline. Nine patients (69.2%) developed gamma globulin above the upper limit of normal (i.e., > 1.5 g/dL) which was not present at baseline. A correlation between gamma globulin elevations and antibody titers to PAP-GM-CSF in these patients (n = 9) was observed at Week 6 (r = 0.664, P = 0.051). These data demonstrate that elevated gamma globulin levels can develop following treatment with sipuleucel-T and were associated with the development of an antigen-specific humoral response.
Sims:Dendreon Corp.: Employment. dela Rosa:Dendreon Corp.: Employment. Lin:Dendreon Corp.: Employment. Sheikh:Dendreon Corp.: Employment.
Asterisk with author names denotes non-ASH members.