Heat Shock Protein Vaccine Elicited Immune Response in Glioblastoma

The addition of an autologous tumor derived–heat shock protein vaccination to standard therapy may improve outcomes for patients with glioblastoma, a new study has shown.

According to the study, heat shock protein can be used to deliver tumor antigens for immune stimulation, and phase I and II studies had previously shown robust immune stimulation in response to vaccination for the treatment of glioblastoma.

In this phase II trial, patients treated with the autologous vaccine had a median overall survival of 23.8 months. In addition, the study showed that patients with low programmed death ligand 1 (PD-L1) expression on myeloid cells had improved survival when treated with the vaccine compared with patients with high PD-L1 expression.

“Expression of PD-L1 on circulating myeloid cells in glioblastoma patients appears to impact systemic immunity and the efficacy of vaccination, suggesting a role for anti–PD-L1 therapy in combination with antitumor vaccines,” wrote researcher Orin Bloch, MD, of the department of neurological surgery at Northwestern University in Chicago, and colleagues in Clinical Cancer Research.

The single-arm phase II study included 46 adult patients with glioblastoma who underwent standard care with surgical resection plus radiation and chemotherapy. The patients then received an autologous vaccine generated from their resected tumor delivered in weekly vaccinations after the completion of radiation. The primary endpoint was overall survival.

Patients received a median of nine vaccine doses. At data analysis, 26% of patients were alive and had no evidence of disease progression. The median progression-free survival was 18 months. The median overall survival was 23.8 months with a 3-year survival rate of 32.6%.

The researchers noted that “the greatest improvement in survival was observed during the initial treatment period from surgical resection to first progression.”

MGMT methylation status was also evaluated as a prognostic factor. Median overall survival for MGMT unmethylated tumors was 18 months compared with 44.7 months for MGMT methylated tumors (hazard ratio [HR], 3.9; 95% CI, 1.8–8.8; P < .001). According to the researchers, this suggests “that vaccinated patients may have received some clinical benefit beyond what was expected from chemotherapy alone, based on molecular phenotype.”

Additionally, the researchers looked at survival according to PD-L1 expression on circulating myeloid cells because “expression of PD-L1 on circulating myeloid cells has previously been suggested to be an important contributor to tumor-induced immunosuppression.” The median overall survival for high PD-L1 expressors was 18 months compared with 44.7 months for low PD-L1 expressors (HR, 3.3; 95% CI, 1.4–8.6; P = .007).

Ninety-six percent of patients experienced an adverse event of any kind; 74% of patients had an adverse event attributed to the vaccine, but none were grade 3 or 4.