First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma
Authors: Liau Linda M. , Ashkan Keyoumars , Tran David D. , Campian Jian L. , Trusheim John E. , Cobbs Charles S. , Heth Jason A. , Salacz Michael , Taylor Sarah , D’Andre Stacy D. , Iwamoto Fabio M. , Dropcho Edward J. , Moshel Yaron A. , Walter Kevin A. , Pillainayagam Clement P. , Aiken Robert , Chaudhary Rekha , Goldlust Samuel A. , Bota Daniela A. , Duic Paul , Grewal Jai , Elinzano Heinrich , Toms Steven A. , Lillehei Kevin O. , Mikkelsen Tom , Walbert Tobias , Abram Steven R. , Brenner Andrew J. , Brem Steven , Ewend Matthew G. , Khagi Simon , Portnow Jana , Kim Lyndon J. , Loudon William G. , Thompson Reid C. , Avigan David E. , Fink Karen L. , Geoffroy Francois J. , Lindhorst Scott , Lutzky Jose , Sloan Andrew E. , Schackert Gabriele , Krex Dietmar , Meisel Hans-Jorg , Wu Julian , Davis Raphael P. , Duma Christopher , Etame Arnold B. , Mathieu David , Kesari Santosh , Piccioni David , Westphal Manfred , Baskin David S. , New Pamela Z. , Lacroix Michel , May Sven-Axel , Pluard Timothy J. , Tse Victor , Green Richard M. , Villano John L. , Pearlman Michael , Petrecca Kevin , Schulder Michael , Taylor Lynne P. , Maida Anthony E. , Prins Robert M. , Cloughesy Timothy F. , Mulholland Paul , Bosch Marnix L. 
Published: May 2018

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