Journal of Translational Medicine (May 2018)

First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma

  • Linda M. Liau,
  • Keyoumars Ashkan,
  • David D. Tran,
  • Jian L. Campian,
  • John E. Trusheim,
  • Charles S. Cobbs,
  • Jason A. Heth,
  • Michael Salacz,
  • Sarah Taylor,
  • Stacy D. D’Andre,
  • Fabio M. Iwamoto,
  • Edward J. Dropcho,
  • Yaron A. Moshel,
  • Kevin A. Walter,
  • Clement P. Pillainayagam,
  • Robert Aiken,
  • Rekha Chaudhary,
  • Samuel A. Goldlust,
  • Daniela A. Bota,
  • Paul Duic,
  • Jai Grewal,
  • Heinrich Elinzano,
  • Steven A. Toms,
  • Kevin O. Lillehei,
  • Tom Mikkelsen,
  • Tobias Walbert,
  • Steven R. Abram,
  • Andrew J. Brenner,
  • Steven Brem,
  • Matthew G. Ewend,
  • Simon Khagi,
  • Jana Portnow,
  • Lyndon J. Kim,
  • William G. Loudon,
  • Reid C. Thompson,
  • David E. Avigan,
  • Karen L. Fink,
  • Francois J. Geoffroy,
  • Scott Lindhorst,
  • Jose Lutzky,
  • Andrew E. Sloan,
  • Gabriele Schackert,
  • Dietmar Krex,
  • Hans-Jorg Meisel,
  • Julian Wu,
  • Raphael P. Davis,
  • Christopher Duma,
  • Arnold B. Etame,
  • David Mathieu,
  • Santosh Kesari,
  • David Piccioni,
  • Manfred Westphal,
  • David S. Baskin,
  • Pamela Z. New,
  • Michel Lacroix,
  • Sven-Axel May,
  • Timothy J. Pluard,
  • Victor Tse,
  • Richard M. Green,
  • John L. Villano,
  • Michael Pearlman,
  • Kevin Petrecca,
  • Michael Schulder,
  • Lynne P. Taylor,
  • Anthony E. Maida,
  • Robert M. Prins,
  • Timothy F. Cloughesy,
  • Paul Mulholland,
  • Marnix L. Bosch

DOI
https://doi.org/10.1186/s12967-018-1507-6
Journal volume & issue
Vol. 16, no. 1
pp. 1 – 9

Abstract

Read online

Abstract Background Standard therapy for glioblastoma includes surgery, radiotherapy, and temozolomide. This Phase 3 trial evaluates the addition of an autologous tumor lysate-pulsed dendritic cell vaccine (DCVax®-L) to standard therapy for newly diagnosed glioblastoma. Methods After surgery and chemoradiotherapy, patients were randomized (2:1) to receive temozolomide plus DCVax-L (n = 232) or temozolomide and placebo (n = 99). Following recurrence, all patients were allowed to receive DCVax-L, without unblinding. The primary endpoint was progression free survival (PFS); the secondary endpoint was overall survival (OS). Results For the intent-to-treat (ITT) population (n = 331), median OS (mOS) was 23.1 months from surgery. Because of the cross-over trial design, nearly 90% of the ITT population received DCVax-L. For patients with methylated MGMT (n = 131), mOS was 34.7 months from surgery, with a 3-year survival of 46.4%. As of this analysis, 223 patients are ≥ 30 months past their surgery date; 67 of these (30.0%) have lived ≥ 30 months and have a Kaplan-Meier (KM)-derived mOS of 46.5 months. 182 patients are ≥ 36 months past surgery; 44 of these (24.2%) have lived ≥ 36 months and have a KM-derived mOS of 88.2 months. A population of extended survivors (n = 100) with mOS of 40.5 months, not explained by known prognostic factors, will be analyzed further. Only 2.1% of ITT patients (n = 7) had a grade 3 or 4 adverse event that was deemed at least possibly related to the vaccine. Overall adverse events with DCVax were comparable to standard therapy alone. Conclusions Addition of DCVax-L to standard therapy is feasible and safe in glioblastoma patients, and may extend survival. Trial registration Funded by Northwest Biotherapeutics; Clinicaltrials.gov number: NCT00045968; https://clinicaltrials.gov/ct2/show/NCT00045968?term=NCT00045968&rank=1; initially registered 19 September 2002

Keywords