Heat-shock protein peptide complex-96 vaccination for recurrent glioblastoma: a phase II, single-arm trial

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. In this open-label, single-arm, phase I...

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Published in:Neuro-oncology (Charlottesville, Va.) Va.), 2014-01, Vol.16 (2), p.274-279
Main Authors: Bloch, Orin, Crane, Courtney A, Fuks, Yelena, Kaur, Rajwant, Aghi, Manish K, Berger, Mitchel S, Butowski, Nicholas A, Chang, Susan M, Clarke, Jennifer L, McDermott, Michael W, Prados, Michael D, Sloan, Andrew E, Bruce, Jeffrey N, Parsa, Andrew T
Format: Article
Language:English
Subjects:
Adult
Aged
Brain Neoplasms - drug therapy
Brain Neoplasms - mortality
Brain Neoplasms - pathology
Cancer Vaccines - therapeutic use
Clinical Research
Female
Follow-Up Studies
Glioblastoma - drug therapy
Glioblastoma - mortality
Glioblastoma - pathology
Heat-Shock Proteins - therapeutic use
Humans
Male
Middle Aged
Neoplasm Recurrence, Local - drug therapy
Neoplasm Recurrence, Local - pathology
Neoplasm Staging
Prognosis
Survival Rate
Vaccination
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Summary: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. 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. 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. 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.
ISSN:1522-8517
1523-5866
DOI:10.1093/neuonc/not203