Heat-shock protein peptide complex-96 vaccination for recurrent glioblastoma: a phase II, single-arm trial
Heat-shock protein peptide complex-96 vaccination for recurrent glioblastoma: a phase II, single-arm trial
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DOI：
10.1093/neuonc/not203
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发表时间：
2014-02-01
期刊：
影响因子：
15.9
通讯作者：
Parsa, Andrew T.
中科院分区：
文献类型：
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作者：
Bloch, Orin;Crane, Courtney A.;Parsa, Andrew T.
背景。复发性多形性胶质母细胞瘤（GBM）患者的预后较差，免疫疗法可能会改善其预后。我们研究了一种自体热休克蛋白肽复合物 -96（HSPPC - 96）疫苗用于复发性GBM患者的安全性和有效性。
方法。在这项开放标签、单臂、II期研究中，患有可手术切除的复发性GBM的成年患者在大体全切术后接种疫苗。主要终点是6个月时的总生存率。次要终点包括总生存率、无进展生存率、安全性和免疫分析。在意向性治疗人群和有效人群中进行了结果分析。
结果。在2007年10月3日至2011年10月24日期间，41例患者接受了复发性GBM的大体全切术，并接受了中位数为6剂的HSPPC - 96疫苗。治疗后，90.2%的患者在6个月时存活（95%置信区间[CI]：75.9 - 96.8），29.3%的患者在12个月时存活（95%CI：16.6 - 45.7）。中位总生存期为42.6周（95%CI：34.7 - 50.5）。27例（66%）患者在治疗前存在淋巴细胞减少，淋巴细胞计数低于队列中位数的患者总生存期降低（风险比：4.0；95%CI：1.4 - 11.8；P = 0.012）。没有治疗相关的死亡。报告了37例严重（3 - 5级）不良事件，其中17例归因于手术切除，1例3级全身性事件与疫苗相关。
结论。HSPPC - 96疫苗是安全的，值得进一步研究其治疗复发性GBM的有效性。治疗前显著的淋巴细胞减少可能影响免疫疗法的结果，值得进一步研究。
Background. Outcomes for patients with recurrent glioblastoma multiforme (GBM) are poor and may be improved by immunotherapy. We investigated the safety and efficacy of an autologous heat-shock protein peptide complex -96 (HSPPC-96) vaccine for patients with recurrent GBM.Methods. In this open-label, single-arm, phase II study, adult patients with surgically resectable recurrent GBM were given vaccine after gross total resection. The primary endpoint was overall survival at 6 months. Secondary endpoints included overall survival, progression-free survival, safety, and immune profiling. Outcome analyses were performed in the intention-to-treat and efficacy populations.Results. Between October 3, 2007 and October 24, 2011, 41 patients underwent gross total resection of recurrent GBM and received a median of 6 doses of HSPPC-96 vaccine. Following treatment, 90.2% of patients were alive at 6 months (95% confidence interval [CI]: 75.9-96.8) and 29.3% were alive at 12 months (95% CI: 16.6-45.7). Median overall survival was 42.6 weeks (95% CI: 34.7 - 50.5). Twenty-seven (66%) patients were Lymphopenic prior to therapy, and patients with lymphocyte counts below the cohort median demonstrated decreased overall survival (hazard ratio: 4.0; 95% CI: 1.4-11.8; P = .012). There were no treatment-related deaths. There were 37 serious (grades 3-5) adverse events reported, with 17 attributable to surgical resection and a single grade 3 constitutional event related to the vaccine.Conclusion. The HSPPC-96 vaccine is safe and warrants further study of efficacy for the treatment of recurrent GBM. Significant pretreatment lymphopenia may impact the outcomes of immunotherapy and deserves additional investigation.