Specialty:

Neurological Surgery

Keywords:

Glioblastoma, immunotherapy, dendritic cells, vaccines

Background:

Glioblastomas (GBM) are the most common malignant brain tumors and are some of the most aggressive and lethal forms of cancers that can arise in humans. Standard of care for newly diagnosed GBMs include surgery, radiotherapy, and chemotherapy. A novel treatment is the autologous tumor lysate-loaded dendritic cell vaccine (DCVax-L), which has been tested in clinical trials in combination with standard of care for patients with GBM. DCVax-L uses the patient’s autologous dendritic cells to present tumor antigens to the immune system, prime host T cells, and mobilize antitumor responses. An international, multi-center Phase 3 clinical trial using DCVax-L in adjunct with standard treatment (medication, radiation, surgery) was conducted with a total of 331 patients. When compared with external case-matched controls, survival at 24 and 30 months was 20.7% vs 9.6% and 11.1% vs 5.1%, respectively.

Objective:

The objective of this study was to evaluate the characteristics of the long-term survivors who received DCVax-L and elucidated potential prognostic/predictive markers of long-term survival in particular subgroups of patients.

Methods and Results:

We performed survival analysis on the UCLA cohort of patients who received autologous tumor lysate-pulsed DC vaccines (n=76) to determine whether undetermined patient factors had an impact on survival length. Descriptive analysis showed no difference between patients with regards to demographic parameters (age, sex, race, ethnicity, comorbidities). Univariate analysis demonstrated a significant difference in MGMT methylation (p=0.02) between patients who survived 3 years or longer versus those who died earlier. Multivariate analysis utilizing 3 separate models incorporating 3 varied sets of confounding variables continued to show a correlation between MGMT methylation (p=0.03, p=0.03) and long-term survival.

Conclusions:

We determined that MGMT methylation was correlated with improved survival in patients diagnosed with glioblastoma. We believe MGMT methylation may be a surrogate marker of a favorable response to immunotherapy, and further validation studies are warranted.