Glioblastoma survival benefit with vaccination, chemotherapy combination
medwireNews: Treatment with a cytomegalovirus (CMV)-targeted dendritic cell (DC)-based vaccine together with dose-intensified temozolomide (DI-TMZ) leads to improved survival in patients with newly diagnosed glioblastoma relative to historic controls given standard therapy, findings indicate.
The team from Duke University Medical Center in Durham, North Carolina, USA, explains that CMV proteins have been detected in over 90% of sampled glioblastomas, with the expression restricted to glioma cells, providing “an unparalleled opportunity to subvert cytomegalovirus antigens as tumor-specific targets.”
The study enrolled 12 patients with stage IV disease who did not have disease progression after completing standard treatment comprising gross total resection followed by 6 weeks of radiation therapy and concurrent TMZ at a dose of 75 mg/m2 per day.
After a 4-week break, the study participants received DI-TMZ (100 mg/m2 daily) for 21 days of a 28-day cycle, after which they were given three courses of a DC-based vaccine targeting the CMV pp65 antigen admixed with granulocyte macrophage colony-stimulating factor (GM-CSF) at a dose of 150 μg. Subsequently, patients who had not progressed continued to receive monthly cycles of DI-TMZ alongside the vaccine at their physician’s discretion for a total of 6–12 cycles.
Participants who completed three vaccine courses had a median progression-free survival (PFS) and overall survival (OS) of 25.3 and 41.1 months, respectively. These were significantly longer than the corresponding median times, at 8.0 and 19.2 months, for 23 historical controls matched for age, gender, tumor, and standard of care therapy.
By contrast, the one patient who did not receive all three initial vaccinations experienced disease progression at 5.3 months and died at 9.4 months from diagnosis.
Additionally, all 11 patients who completed three vaccine courses had better survival than that predicted by the recursive partitioning analysis classification, with a median gain of 30 months, John Sampson and co-researchers report.
They also point out that four patients were progression-free at 59 to 64 months after resection.
Noting that median survival in this population is 15 months, the study authors say that the “unexpectedly prolonged” survival in their study is unlikely to be attributable just to DI-TMZ as a recent phase III trial showed “no survival benefit of the same DI-TMZ regimen over standard-temozolomide across all subgroups of patients with newly diagnosed glioblastoma.”
Moreover, the improvement in survival occurred despite an increase in the proportion and proliferation of regulatory T cells after the first DI-TMZ cycle.
There were no toxicities related to the cellular portion of the vaccine, but one patient had a grade 3 immunologic reaction to GM-CSF administration.
Sampson et al write in Clinical Cancer Research that this study confirms their previous results that “cytomegalovirus pp65 represents a targetable axis in newly diagnosed glioblastoma resulting in patient survival far exceeding that of predicted outcomes and observed rates in historical controls.”
And they conclude: “What remains to be determined is whether this combinatorial regimen is strictly dependent on antigen specificity, a question that is best suited for future randomization studies.”
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