In an externally controlled phase III trial reported in JAMA Oncology, Liau et al found that the addition of an autologous tumor lysate–loaded dendritic cell vaccine (DCVax-L) to standard of care improved survival in patients with newly diagnosed glioblastoma and recurrent glioblastoma compared with contemporaneous external control patients receiving standard of care.
Study Details
The study included 232 patients with resected newly diagnosed glioblastoma and 64 with recurrent glioblastoma in first relapse from sites in four countries who received DCVax-L plus standard of care between August 2007 and November 2015. Standard of care consisted of temozolomide in patients with newly diagnosed glioblastoma and lomustine, bevacizumab, or best supportive care in patients with recurrent glioblastoma. Patients received DCVax-L on days 0, 10, and 20 and in months 2, 4, 8, 12, 18, 24, and 30; each dose consisted of intradermal injection of 2.5 million dendritic cells. Outcomes were compared with those in contemporaneous control populations of 1,366 patients with newly diagnosed glioblastoma receiving standard of care in 5 randomized trials and 640 with recurrent glioblastoma in first relapse treated with standard of care in the control groups of 10 randomized trials.
Key Findings
Median overall survival was 19.3 months (95% confidence interval [CI] = 17.5–21.3 months) among the 232 patients with newly diagnosed glioblastoma receiving DCVax-L vs 16.5 months (95% CI = 16.0–17.5) in external control patients (hazard ratio [HR] = 0.80, 98% CI = 0.00–0.94, P = .002). Rates at 48 and 60 months were 15.7% vs 9.9% and 13.0% vs 5.7%.
Median overall survival was 30.2 months (95% CI = 23.7–33.9 months) among 90 patients with newly diagnosed glioblastoma receiving DCVax-L and 21.3 months (95% CI = 18.3–25.1 months) among 199 control patients with methylated MGMT (HR = 0.74, 95% CI = 0.55–1.00, P = .03).
Median overall survival from relapse was 13.2 months (95% CI = 9.7–16.8 months) among 64 patients with recurrent glioblastoma receiving DCVax-L vs 7.8 months (95% CI = 7.2–8.2 months) among external control patients (HR = 0.58, 98% CI = 0.00–0.76, P < .001). Rates at 24 and 30 months were 20.7% vs 9.6% and 11.1% vs 5.1%.
A total of 2,151 doses of DCVax-L were administered. A total of five serious adverse events considered at least possibly related to the vaccine were observed, consisting of three cases of intracranial edema (two at grade 3, one at grade 2), one case of nausea (grade 3), and one case of lymph node infection (grade 3). No evidence of autoimmune reactions or cytokine storm was observed.
The investigators concluded, “In this study, adding DCVax-L to standard of care resulted in clinically meaningful and statistically significant extension of survival for patients with both newly diagnosed glioblastoma and recurrent glioblastoma compared with contemporaneous, matched external controls who received standard of care alone.”
Marnix L. Bosch, PhD, of Northwest Biotherapeutics, Inc, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by Northwest Biotherapeutics, Inc. For full disclosures of the study authors, visit jamanetwork.com.
