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

Abstract

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.

• Authors: Orin Bloch, Courtney A Crane, Yelena Fuks, Rajwant Kaur, Manish K Aghi, Mitchel S Berger, Nicholas A Butowski, Susan M Chang, Jennifer L Clarke, Michael W McDermott, Michael D Prados, Andrew E Sloan, Jeffrey N Bruce, Andrew T Parsa
• Journal: Neuro-oncology (Neuro Oncol) Vol. 16 Issue 2 Pg. 274-9 (Jan 2014) ISSN: 1523-5866 [Electronic] England
• PMID: 24335700 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cancer Vaccines
• Heat-Shock Proteins
• vitespin

Topics

• Adult
• Aged
• Brain Neoplasms (drug therapy, mortality, pathology)
• Cancer Vaccines (therapeutic use)
• Female
• Follow-Up Studies
• Glioblastoma (drug therapy, mortality, pathology)
• Heat-Shock Proteins (therapeutic use)
• Humans
• Male
• Middle Aged
• Neoplasm Recurrence, Local (drug therapy, pathology)
• Neoplasm Staging
• Prognosis
• Survival Rate
• Vaccination