Sipuleucel-T is an autologous cellular immunotherapy for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer (mCRPC). 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. Three randomized Phase 3 studies have been completed in mCRPC patients, the largest of which was the IMPACT study. In the IMPACT study, 512 patients were randomized (2:1) to sipuleucel-T or control (non-activated autologous PBMCs). Complete blood counts were performed at Baseline and Weeks 6, 14, and 26, which included total white blood cell counts and eosinophil counts. Laboratory values for time points were categorized as low, normal, or high using the normal range for each laboratory test. A higher percentage of patients randomized to sipuleucel-T developed mild and transient elevations in eosinophil counts versus patients randomized to control. At Week 6, 26.3% (72/274) of sipuleucel-T patients with a normal baseline eosinophil count had an elevated eosinophil count compared with 0.7% (1/145) of control patients. By Week 14, 2.1% (4/193) of sipuleucel-T patients with a normal baseline eosinophil count had an elevated eosinophil count compared with 0% (0/93) control patients. Sipuleucel-T treated patients showed robust antigen specific antibody responses against the immunizing antigen at Weeks 6, 14, and 26. There was a positive correlation between the change in eosinophil count from baseline and the magnitude of the immune response (r = 0.189 at Week 6, r = 0.289 at Week 14, and r = 0.279 at Week 26). There was also a positive correlation between the magnitude of eosinophil count increase and the magnitude of increase in the serum cytokines IL2, IL5, and thymus and activated-regulated chemokine (TARC) in the weeks following treatment with sipuleucel-T. Patients who developed eosinophilia compared with those who did not experienced a higher frequency of some events associated with infusion reactions, such as chills (67.7% vs. 51.4%), pyrexia (41.9% vs. 30.1%), and headache (30.6% vs. 16.7%), but otherwise eosinophilia did not appear to be generally associated with clinical consequences, and there were no cases of hypereosinophilic syndrome reported. There was a positive correlation noted between the magnitude of increase in eosinophil count from baseline and overall survival in sipuleucel-T patients from the 3 mCRPC Phase 3 studies (N = 431, HR = 0.627, P = 0.012). In summary, transient elevated eosinophil counts have been noted in approximately 25% of patients who receive sipuleucel-T, and were associated with an immune response to the immunizing antigen, higher serum levels of the cytokines IL2, IL5 and TARC, and prolonged overall survival.
Sims:Dendreon Corp.: Employment. Lin:Dendreon Corp.: Employment. dela Rosa:Dendreon Corp.: Employment. Sheikh:Dendreon Corp.: Employment. Whitmore:Dendreon Corp.: Employment. Frohlich:Dendreon Corp.: Employment.
Asterisk with author names denotes non-ASH members.