Pro-vax.

Top Line: Vaccines remain a tantalizing potential therapeutic for glioblastoma multiforme (GBM).

The Study: In the largest study of its kind to date, this phase 3 international trial spanning 94 centers across 4 countries demonstrates the efficacy of an autologous tumor lysate-loaded dendritic cell vaccine (DCVax-L). Come again? A patient’s own dendritic cells are removed via leukapheresis and primed ex vivo against her own broken down GBM cells (aka tumor lysate) removed at initial surgery. The beauty is “using autologous rather than standardized antigens addresses the extreme heterogeneity of glioblastoma and can ensure that the treatment is targeting antigens actually present on the patient’s tumor.” It also addressed heterogeneity and treatment evasion within a single patient’s tumor by exposing ex vivo dendritic cells to the whole shebang of his own tumor antigens, not just the most common ones. In addition to standard of care, 331 patients with newly diagnosed GBM were enrolled and randomized 2:1 to DCVax-L versus placebo on days 0, 10, and 20, then in months 2, 4, 8, 12, 18, 24, and 30. The primary endpoint of overall survival was significantly improved from a median of 16.5 → 19.3 months with the addition of DCVax-L. At five years, rates of survival more than doubled from 6 → 13%. And that is with two-thirds (n=64) of the placebo arm crossing over to the vaccine arm upon recurrence/progression. In fact, these 64 patients also saw a survival advantage with salvage use of the vaccine when compared with matched contemporaneous controls.

TBL: An autologous tumor lysate-loaded dendritic cell vaccine (does that term make sense now…?) may improve survival when added to other standard therapies for newly-diagnosed and recurrent GBM.  | Liau, JAMA Oncol 2022