Dendritic cell vaccination improves survival in glioblastoma
Oncology
Los Angeles – Vaccination with autologous dendritic cells containing tumor lysate, in addition to standard therapy, may significantly improve both clinical and statistically significant survival in newly diagnosed and recurrent glioblastoma patients. This conclusion comes from a prospective phase III study in JAMA Oncology (2022; DOI: 10.1001/jamaoncol.2022.5370).
Dendritic cell vaccination is a form of active immunotherapy. “Dendritic cells present tumor antigens to the immune system to activate it specifically against the tumor. It is believed to trigger an anti-tumor immune response, ultimately leading to the destruction of tumor cells,” explain the authors led by Linda M. Liau from the Department of Neurosurgery at the University of California, Los Angeles, USA.
The study was conducted in the USA, Canada, UK, and Germany. Patients – in addition to standard therapy with temozolomide – were randomly assigned to receive either immunization with mature dendritic cells containing tumor lysate (DCVax-L) or placebo.
Comparison with an External Control Group is Required
As too many patients (64 out of 99) in the placebo group also received DCVax-L after recurrence, they could not be considered as a comparison group. Thus, the control consisted of 1366 contemporary, external, newly diagnosed glioblastoma patients treated with standard therapy.
A total of 331 patients were included in the study, of which 232 received DCVax-L and 99 received placebo. The 232 patients with newly diagnosed glioblastoma who received DCVax-L survived on average 19.3 months after randomization. In the control group, this was 16.5 months (HR 0.80; p = 0.002).
Clear Effect on Overall Survival
At 48 months after randomization, the overall survival in the DCVax-L group was 15.7% compared to 9.9% in the placebo group. At 60 months, 13.0% of patients in the DCVax-L group were still alive, compared to 5.7% in the placebo group.
The overall survival of 64 patients with recurrent glioblastoma who switched from the placebo group to the DCVax-L group was 13.2 months (from the time of recurrence). The corresponding survival duration in the external control patients was 7.8 months (HR 0.58; p <0.001).
Survival at 24 months after recurrence was 20.7% in the DCVax-L group and 9.6% in the control group. At 30 months, these figures were 11.1% and 5.1%, respectively.
Subgroup analysis showed that patients with newly diagnosed glioblastoma with methylated MGMT promoter who received DCVax-L had improved survival compared to control patients (HR 0.74; p = 0.03).
Liau and her colleagues report that patients tolerated DCVax-L well. Serious adverse effects were observed in 5 out of 2151 doses administered, which could be related to DCVax-L.
These included 3 cases of brain edema, 1 case of severe nausea, and 1 case of lymph node infection. There was no evidence of autoimmune reactions or cytokine storms in any of the patients receiving DCVax-L.