Association of Autologous Tumor Lysate-Loaded Dendritic Cell Vaccination With Extension of Survival Among Patients With Newly Diagnosed and Recurrent Glioblastoma

Abstract

ImportanceGlioblastoma is the most lethal primary brain cancer. Clinical outcomes for glioblastoma remain poor, and new treatments are needed.ObjectiveTo investigate whether adding autologous tumor lysate-loaded dendritic cell vaccine (DCVax-L) to standard of care (SOC) extends survival among patients with glioblastoma.Design, Setting, and ParticipantsThis phase 3, prospective, externally controlled nonrandomized trial compared overall survival (OS) in patients with newly diagnosed glioblastoma (nGBM) and recurrent glioblastoma (rGBM) treated with DCVax-L plus SOC vs contemporaneous matched external control patients treated with SOC. This international, multicenter trial was conducted at 94 sites in 4 countries from August 2007 to November 2015. Data analysis was conducted from October 2020 to September 2021.InterventionsThe active treatment was DCVax-L plus SOC temozolomide. The nGBM external control patients received SOC temozolomide and placebo; the rGBM external controls received approved rGBM therapies.Main Outcomes and MeasuresThe primary and secondary end points compared overall survival (OS) in nGBM and rGBM, respectively, with contemporaneous matched external control populations from the control groups of other formal randomized clinical trials.ResultsA total of 331 patients were enrolled in the trial, with 232 randomized to the DCVax-L group and 99 to the placebo group. Median OS (mOS) for the 232 patients with nGBM receiving DCVax-L was 19.3 (95% CI, 17.5-21.3) months from randomization (22.4 months from surgery) vs 16.5 (95% CI, 16.0-17.5) months from randomization in control patients (HR = 0.80; 98% CI, 0.00-0.94; P = .002). Survival at 48 months from randomization was 15.7% vs 9.9%, and at 60 months, it was 13.0% vs 5.7%. For 64 patients with rGBM receiving DCVax-L, mOS was 13.2 (95% CI, 9.7-16.8) months from relapse vs 7.8 (95% CI, 7.2-8.2) months among control patients (HR, 0.58; 98% CI, 0.00-0.76; P < .001). Survival at 24 and 30 months after recurrence was 20.7% vs 9.6% and 11.1% vs 5.1%, respectively. Survival was improved in patients with nGBM with methylated MGMT receiving DCVax-L compared with external control patients (HR, 0.74; 98% CI, 0.55-1.00; P = .03).Conclusions and RelevanceIn this study, adding DCVax-L to SOC resulted in clinically meaningful and statistically significant extension of survival for patients with both nGBM and rGBM compared with contemporaneous, matched external controls who received SOC alone.Trial RegistrationClinicalTrials.gov Identifier: NCT00045968

Recurrent Glioblastoma: Ongoing Clinical Challenges and Future Prospects

“… 122 In a recent report the 64 patients with recurrent WBC who crossed over to DCVAX treatment had an mOS of 13.2 (95% CI, 9.7–16.8) months from relapse vs 7.8 (95% CI, 7.2–8.2) months among control patients (HR, 0.58; 98% CI, 0.00–0.76; P < 0.001). 123 Methodological problems in the study design obscure these results. 124 ICT-107 is an autologous dendritic cell vaccine pulsed with six synthetic peptide epitopes targeting GB tumor/stem cell-associated antigens (MAGE-1, HER-2, AIM-2, TRP-2, gp100, and IL13Ra2).…”

Next-generation antigen-presenting cell immune therapeutics for gliomas

“…This randomized trial reported that DCVax-L, in combination with standard of care, could significantly extend the survival of patients with either newly diagnosed or recurrent GBM compared with historical controls. This randomized trial reported that DCVax-L in combination with standard of care could significantly extend the survival of patients with either newly diagnosed or recurrent GBM ( 96 ). Liau’s seminal work paved the way for further development of the field of DC vaccination in GBM.…”

Verlängerung des Gesamtüberlebens durch die Impfung von autologen tumorlysatbeladenen dendritischen Zellen (DCVax-L) bei Patienten mit neu diagnostiziertem und rezidivierendem Glioblastom

“…Das Glioblastom gilt allgemein als immunologisch „kalte“ Tumorentität – die vergangenen prospektiven, randomisierten immuntherapeutischen Studien wiesen keinen ausschlaggebenden klinischen „benefit“ auf [ 1 , 2 ]. Die vorliegende Studie beschreibt, dass durch die Anwendung eines Vakzins aus autologen tumorlysatbeladenen dendritischen Zellen (DCVax-L) – zusätzlich zur Standardtherapie – eine Verbesserung des Gesamtüberlebens (mOS) bei Patienten mit nGBM wie auch mit rGBM nach Cross-over erreicht werden kann [ 3 ]. Die Möglichkeit des Cross-overs im Studiendesgin wurde laut Autoren hierbei von der FDA gewünscht.…”