Impact of prior radiation treatment (tx) on sipuleucel-T (sip-T) product parameters in PROCEED patients (pts).

Abstract

183 Background: Sipuleucel-T (sip-T) is an autologous cellular immunotherapy indicated for asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer. Approval of sip-T was based primarily on the randomized, controlled, phase 3 study (IMPACT) that demonstrated a 22% reduction in the risk of death. Since radiation tx could suppress bone marrow function and therefore immune function, IMPACT excluded patients (pts) who received radiation more than or equal to 28 days prior to registration. PROCEED is an ongoing phase 4 registry enrolling pts tx with commercial sip-T in the real-world setting. Palliative radiation (PR) tx for bone pain prior to sip-T is not restricted in PROCEED, so the effects of prior radiation on sip-T manufacturing parameters can be evaluated. Methods: Pts treated with sip-T at or before six months were eligible. Baseline pt demographics and disease characteristics were collected. Sip-T product parameters that were assessed included: total nucleated cell (TNC) count, antigen presenting cell (APC) count (large CD54+cells), and APC activation (upregulation of CD54; a measure of product potency). Results: Data were available for 1,244 pts enrolled by May 2013, who completed tx; of those, 112 (9.0%) pts received PR to bone metastases prior to sip-T and 517 (41.6%) pts had no prior radiation of any kind (NRT). To ensure that groups (grp) were homogeneous and to limit the comparison of NRT pts with those who had PR only for bone metastases, pts with radical prostatectomy were isolated from each grp for further study, resulting in 44 pts in the PR grp and 159 pts in the NRT grp. Median cumulative APC counts were similar between grp, however TNC counts (PR: 9.89 vs. NRT: 12.09 x 109; P=0.002) and APC activation (PR: 34.2 vs. NRT: 38.5; P=0.048) were lower in the PR grp. However, the percentage of pts receiving all three infusions in each group was comparable (PR: 93.2% vs NRT: 95.0%; P=0.71). Conclusions: In the real-world setting, there is no evidence that prior radiation inhibits successful production of sip-T. Although TNC counts and APC activation were lower, APC counts were comparable in radiation treated pts. Effects on in vivo post treatment immune measures are being collected prospectively in a companion trial called PRIME. Clinical trial information: NCT01306890.