摘要

PURPOSE:This phase II open-label study evaluated the effect of concurrent or sequential administration of abiraterone acetate plus prednisone (AA + P) on sipuleucel-T manufacture and immune responses in metastatic castration-resistant prostate cancer (mCRPC) patients.
EXPERIMENTAL DESIGN:mCRPC patients received sipuleucel-T followed by AA + P 1 day (concurrent) or 10 weeks (sequential) after the first sipuleucel-T infusion. AA + P treatment continued for 26 weeks. The primary endpoint was cumulative antigen presenting cell (APC) activation, and secondary endpoints included cumulative APC number and total nucleated cell counts. Additional endpoints included in vivo peripheral immune responses to sipuleucel-T (T-cell responses, T-cell proliferation, humoral responses, and antigen spread) as well as safety.
RESULTS:Sixty-nine mCRPC patients were enrolled, with 35 and 34 patients randomized to the concurrent and sequential arms, respectively. Ex vivo APC activation was significantly greater at the second and third infusions compared with baseline in both arms (P < 0.05), indicative of an immunologic prime-boost effect. In both arms, sipuleucel-T product parameter profiles and peripheral immune responses were consistent with previously conducted sipuleucel-T phase III trials. Antigen spread was similarly observed in both arms and consistent with the other immunologic endpoints.
CONCLUSIONS:These data suggest that sipuleucel-T can be successfully manufactured during concurrent administration of AA + P without blunting immunologic effects or altering immune parameters that correlate with sipuleucel-T's clinical benefit. Combination of these agents was well tolerated, with no new safety signals emerging.

译文

目的: 这项 II 期开放标签研究评估了同时或连续服用醋酸阿比特龙加泼尼松 (AA P) 的效果关于转移性去势抵抗性前列腺癌 (mCRPC) 患者的 sipuleucel-T 制造和免疫反应。
实验设计: mCRPC 患者接受 sipuleucel-T，然后在第一次 sipuleucel-T 输注后 1 天 (同时) 或 10 周 (连续) 进行 AA P。AA P 治疗持续 26 周。主要终点是累积抗原呈递细胞 (APC) 激活，次要终点包括累积 APC 数量和总有核细胞计数。其他终点包括对 sipuleucel-T 的体内外周免疫反应 (T 细胞反应、 T 细胞增殖、体液反应和抗原扩散) 以及安全性。
结果: 69 例 mCRPC 患者被纳入研究，其中 35 例和 34 例患者分别随机分配到并行组和序贯组。与双臂基线相比，第二次和第三次输注时的体外 APC 活化显著增加 (P & lt; 0.05)，表明免疫素增强效应。在两组中，sipuleucel-T 产品参数分布和外周免疫反应与先前进行的 sipuleucel-T III 期试验一致。在双臂中同样观察到抗原扩散，并与其他免疫终点一致。
结论: 这些数据表明，在 AA P 的同时给药过程中，sipuleucel-T 可以成功制造，而不会减弱免疫效应或改变与 sipuleucel-T 的临床益处相关的免疫参数。这些药物的组合耐受性良好，没有新的安全信号出现。