Dendritic Cell Vaccination Meaningfully Improves Survival Outcomes in Newly Diagnosed and Recurrent Glioblastoma

Treatment with autologous tumor lysate­–loaded dendritic cell vaccine (DCVax-L) plus standard-of-care temozolomide (Temodar) in patients with newly diagnosed or recurrent glioblastoma significantly prolonged survival vs standard-of-care therapy, according to findings from a phase 3 trial (NCT00045968) published recently in JAMA Oncology.

Median overall survival (OS) across the 232 patients with newly diagnosed glioblastoma who received DCVax-L was 19.3 months (95% CI, 17.5-21.3) from randomization and 22.4 months from surgery compared with 16.5 months (95% CI, 16.0-17.5) from randomization in the control group (HR 0.80; 98% CI, 0.00-0.94; P = .002). The survival rate was 15.7% at 48 months and 13.0% at 60 months from randomization in the experimental group vs 9.9% and 5.7%, respectively, in the matched control group.

Additionally, among the 64 patients with recurrent disease who received DCVax-L, median OS was 13.2 months (95% CI, 9.7-16.8) from relapse vs 7.8 months (95% CI, 7.2-8.2) in the control group (HR 0.58; 98% CI, 0.00-0.76; P <.001). The corresponding rates of survival at 24 and 30 months after recurrence were 20.7% vs 9.6% and 11.1% vs 5.1% in each respective arm. Patients with newly diagnosed glioblastoma and methylated O6-methylguanine-DNA methyltransferase (MGMT) receiving DCVax-L also had improved survival vs external control patients (HR 0.74; 98% CI, 0.55-1.00; P = .03).

Overall, DCVax-L treatment was associated with a 20% relative reduction in risk of death, the benefit of which increased over time.

“Glioblastomas are aggressive, extremely heterogeneous, immunologically ‘cold,’ and rapidly lethal. There is a pressing need for new treatments and for novel clinical trial designs to streamline their development,” the investigators wrote. “This trial tested a novel fully personalized active immunotherapy. The trial also implemented an innovative design that could help accelerate advances in the field.”

The prospective, externally controlled, nonrandomized trial enrolled 331 patients with newly diagnosed glioblastoma from August 2007 to November 2015. The median age was 56 years (range, 19-73). Most patients were men (61.0%) and White (88.8%). The financial crisis led to the suspension of screening and enrollment from 2008 through 2011. Limited enrollment resumed in 2012, and a total of 303 of 331 patients (91.5%) enrolled from 2012 to 2015. A total of 232 patients were randomly assigned to receive the initial DCVax-L treatment, with the remaining 99 assigned to placebo. After recurrence, a total of 64 of 99 patients in the placebo group crossed over to receive DCVax-L. The trial population was compared with a contemporaneous matched external control population (ECP) treated with standard-of-care. The ECPs were identified by an independent expert firm, the York Health Economics Consortium, and included closely matched patients from the control groups of contemporaneous randomized clinical trials.

“Although the absolute survival was greater in patients with positive prognostic factors, the relative survival benefit of DCVax-L vs ECPs was larger in certain patients who generally fare worse with standard of care, including older patients, patients with substantial residual tumor, and patients with recurrent disease,” the investigators concluded. “These encouraging results suggest that cancer vaccines could be relevant for a broad range of clinical settings.”

Patients were intradermally injected in the upper arm with DCVax-L on days 0, 10, and 20, months 2, 4, and 8, and months 12, 18, 24, and 30, at a dose of 2.5 million dendritic cells. Standard of care consisted of monthly temozolomide (Temodar). The placebo consisted of unmanipulated peripheral blood mononuclear cells and was delivered on the same schedule.

Only 5 serious adverse effects (AEs) across a total 2151 delivered doses of DCVax-L were deemed to be possibly related to the treatment. Of these, there were 2 cases of grade 3 intracranial edema and 1 event that was grade 2, a single event of grade 3 nausea , and 1 event of grade 3 lymph node infection. Investigators found no evidence of any autoimmune reactions or cytokine storm among patients receiving the experimental therapy.

Reference

Liau LM, Ashkan K, Brem S, et al. Association of autologous tumor lysate-loaded dendritic cell vaccination with extension of survival among patients with newly diagnosed and recurrent glioblastoma: a phase 3 prospective externally controlled cohort trial. JAMA Oncol. Published online November 17, 2022. doi:10.1001/jamaoncol.2022.5370