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

description: 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