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

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.

SUBMITTER: Liau LM

PROVIDER: S-EPMC5975654 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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

Liau Linda M LM Ashkan Keyoumars K Tran David D DD Campian Jian L JL Trusheim John E JE Cobbs Charles S CS Heth Jason A JA Salacz Michael M Taylor Sarah S D'Andre Stacy D SD Iwamoto Fabio M FM Dropcho Edward J EJ Moshel Yaron A YA Walter Kevin A KA Pillainayagam Clement P CP Aiken Robert R Chaudhary Rekha R Goldlust Samuel A SA Bota Daniela A DA Duic Paul P Grewal Jai J Elinzano Heinrich H Toms Steven A SA Lillehei Kevin O KO Mikkelsen Tom T Walbert Tobias T Abram Steven R SR Brenner Andrew J AJ Brem Steven S Ewend Matthew G MG Khagi Simon S Portnow Jana J Kim Lyndon J LJ Loudon William G WG Thompson Reid C RC Avigan David E DE Fink Karen L KL Geoffroy Francois J FJ Lindhorst Scott S Lutzky Jose J Sloan Andrew E AE Schackert Gabriele G Krex Dietmar D Meisel Hans-Jorg HJ Wu Julian J Davis Raphael P RP Duma Christopher C Etame Arnold B AB Mathieu David D Kesari Santosh S Piccioni David D Westphal Manfred M Baskin David S DS New Pamela Z PZ Lacroix Michel M May Sven-Axel SA Pluard Timothy J TJ Tse Victor V Green Richard M RM Villano John L JL Pearlman Michael M Petrecca Kevin K Schulder Michael M Taylor Lynne P LP Maida Anthony E AE Prins Robert M RM Cloughesy Timothy F TF Mulholland Paul P Bosch Marnix L ML

Journal of translational medicine 20180529 1

<h4>Background</h4>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<sup>®</sup>-L) to standard therapy for newly diagnosed glioblastoma.<h4>Methods</h4>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 ...[more]

PMID: 29843811

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Project description:BackgroundPrognosis of patients with glioblastoma multiforme (GBM) remains dismal, with median overall survival (OS) of about 15 months. It is therefore crucial to search alternative strategies that improve these results obtained with conventional treatments. In this context, immunotherapy seems to be a promising therapeutic option. We hypothesized that the addition of tumor lysate-pulsed autologous dendritic cells (DCs) vaccination to maximal safe resection followed by radiotherapy and concomitant and adjuvant temozolomide could improve patients' survival.MethodsWe conducted a phase-II clinical trial of autologous DCs vaccination in patients with newly diagnosed patients GBM who were candidates to complete or near complete resection. Candidates were finally included if residual tumor volume was lower than 1 cc on postoperative radiological examination. Autologous DCs were generated from peripheral blood monocytes and pulsed with autologous whole tumor lysate. The vaccination calendar started before radiotherapy and was continued during adjuvant chemotherapy. Progression free survival (PFS) and OS were analyzed with the Kaplan-Meier method. Immune response were assessed in blood samples obtained before each vaccines.ResultsThirty-two consecutive patients were screened, one of which was a screening failure due to insufficient resection. Median age was 61 years (range 42-70). Karnofsky performance score (KPS) was 90-100 in 29%, 80 in 35.5% and 60-70 in 35.5% of cases. MGMT (O6-methylguanine-DNA-methyltransferase) promoter was methylated in 45.2% of patients. No severe adverse effects related to immunotherapy were registered. Median PFS was 12.7 months (CI 95% 7-16) and median OS was 23.4 months (95% CI 16-33.1). Increase in post-vaccination tumor specific immune response after vaccines (proliferation or cytokine production) was detected in 11/27 evaluated patients. No correlation between immune response and survival was found.ConclusionsOur results suggest that the addition of tumor lysate-pulsed autologous DCs vaccination to tumor resection and combined radio-chemotherapy is feasible and safe. A multicenter randomized clinical trial is warranted to evaluate the potential survival benefit of this therapeutic approach. Trial registration This phase-II trial was registered as EudraCT: 2009-009879-35 and ClinicalTrials.gov Identifier: NCT01006044 retrospectively registered.

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

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

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