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Temozolomide may not be incompatible with immunologic approaches for the treatment of glioblastoma, based on data from an analysis of patients from two ongoing trials.
Vaccination with dendritic cells and either acid-eluted peptides or an antigen-specific peptide has shown promising results in extending survival of patients who have glioblastoma multiforme (GBM). Likewise, temozolomide (Temodar) has been shown to prolong survival in these patients and is part of a standard treatment regimen. Temozolomide, however, often induces a profound and long-lasting lymphopenia that could limit immunotherapeutic approaches.
"This preliminary experience suggests that sequential administration of chemotherapy and immunotherapy may not be deleterious," wrote Dr. John H. Sampson of Duke University in Chapel Hill, N.C., and his colleagues.
The analysis involved patients from two ongoing trials. All were newly diagnosed with GBM, positive for epidermal growth factor receptor variant III (EGFRvIII), and had complete resection.
In the ACTIVATE trial, patients received radiation (approximately 60 Gy) and concurrent temozolomide (50-75 mg/m² per day), followed by vaccination with EGFRvIII-specific peptide. In the ACT II trial, patients received the same radiation and temozolomide regimen. Vaccination was on day 21 of 28-day temozolomide cycles.
Grade 2 lymphopenia was induced in all patients receiving temozolomide after the first cycle. Grade 3 lymphopenia was induced in 70% of patients after the first cycle of temozolomide. However, lymphocyte counts returned to normal after treatment was stopped. "Standard dose temozolomide induces transient but profound lymphodepletion in the majority of patients with GBM," the researchers wrote.
Regulatory T cells increased from 5.2% to 11.8% after temozolomide and radiation. Temozolomide cycles did not appear to have diminished EGFRvIII-specific CD3-positive/CD8-positive T cells producing interferon-g. Further, EGFRvIII-specific IgG responses were induced and maintained during treatment with temozolomide.
"The important fact here is that temozolomide is not contraindicated in immunotherapy and may be beneficial in some of these immune responses," said Dr. Victor A. Levin, a professor of neuro-oncology at the University of Texas M.D. Anderson Cancer Center in Houston, who viewed the data.
Sampson J.H. et al. Temozolomide as a vaccine adjuvant in GBM. Abstract 2020.
Commentary |
This report clearly details that temozolomide can be used in patients receiving vaccine therapy without an adverse effect on the immune system. Indeed, this provocative abstract makes clear that the use of temozolomide, although inducing transient lymphopenia, produces an enhanced specific immune response following recovery from this agent. Accordingly, temozolomide can be used in conjunction with vaccination strategies. Use of this active methylating agent in the treatment of the tumor only increases the potential merit of vaccines that are employed as well. — Henry S. Friedman, M.D.
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