High-Dose Chemotherapy Plus Vaccine Increases Survival in Glioblastoma

An investigational vaccine combined with the chemotherapy drug temozolomide (Temodar) increased survival and was well-tolerated in patients with glioblastoma in a phase 1 trial.

The investigators treated 11 patients as part of a single-arm study to test the safety of a dose-intensified regimen of temozolomide plus a dendritic cell vaccine that selectively targets a cytomegalovirus (CMV) protein.

The dendritic cell vaccine was used in earlier clinical trials to teach T cells to attack tumor cells. The findings suggest that the vaccines could be enhanced when primed by an immune system booster.

In a separate clinical trial, investigators found that higher doses of temozolomide plus an immune-stimulating factor could also prime the immune system and enhance the response of a different vaccine target.

In the current study, published in Clinical Cancer Research, the investigators built upon findings from the earlier clinical trials. They administered a combination of dendritic cell vaccine therapy and the immune-stimulating factor as injections following a dose-intensified regimen of temozolomide. Each participant received a minimum of 6 vaccine treatments, according to the study.

“Our strategy was to capitalize on the immune deficiency caused by the temozolomide regimen,” said lead author Kristen Batich, MD, PhD. “It seems counter-intuitive, but when the patient’s lymphocytes are depleted, it’s actually an optimal time to introduce the vaccine therapy. It basically gives the immune system marching orders to mount resources to attack the tumor.”

Typically, glioblastoma tumors begin to regrow after standard treatment at a median of 8 months, according to the authors. But in the new study, recurrence occurred at a median of 25 months.

Overall, 4 of 11 study participants survived for more than 5 years following the combination treatment, demonstrating that the treatment significantly slowed tumor progression.

“This is a small study, but it’s one in a sequence of clinical trials we have conducted to explore the use of an immunotherapy that specifically targets a protein on glioblastoma tumors,” Batich said. “While not a controlled efficacy study, the survival results were surprising, and they suggest the possibility that combining the vaccine with a more intense regimen of this chemotherapy promotes a strong cooperative benefit.”

Although the findings are promising, the authors stressed that more research needs to be done.

“These are surprisingly promising clinical outcomes,” said senior author John Sampson, MD, PhD. “However, it is important to emphasize that this was a very small study that used historical comparisons rather than randomizing patients to 2 different treatments, but the findings certainly support further study of this approach in larger, controlled clinical trials.”

To date, the investigators have received approval to launch a new study comparing the standard dose of temozolomide versus the dose-intensified regimen plus the vaccine in patients with glioblastoma.