title: 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.
  
  
  CONCLUSIONS
  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: Corresponding Author: Andrew T. Parsa, MD, PhD, Professor and Chair, Department of Neurological Surgery, Northwestern University, Feinberg School of Medicine, 676 N. St. Clair Street, Suite 2210, Chicago, IL 60611. aparsa@nmff.org.
authors: Orin
authors: O
authors: Bloch
authors: Courtney A
authors: CA
authors: Crane
authors: Yelena
authors: Y
authors: Fuks
authors: Rajwant
authors: R
authors: Kaur
authors: Manish K
authors: MK
authors: Aghi
authors: Mitchel S
authors: MS
authors: Berger
authors: Nicholas A
authors: NA
authors: Butowski
authors: Susan M
authors: SM
authors: Chang
authors: Jennifer L
authors: JL
authors: Clarke
authors: Michael W
authors: MW
authors: McDermott
authors: Michael D
authors: MD
authors: Prados
authors: Andrew E
authors: AE
authors: Sloan
authors: Jeffrey N
authors: JN
authors: Bruce
authors: Andrew T
authors: AT
authors: Parsa
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006360:Heat-Shock Proteins / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D014611:Vaccination
chemical_list: D019496:Cancer Vaccines; D006360:Heat-Shock Proteins; C484813:vitespin
keywords: glioblastoma; heat-shock proteins; immunotherapy