CHICAGO — Temozolomide may not be incompatible with immunologic approaches for the treatment of glioblastoma, based on data from a small analysis presented at the annual meeting of the American Society of Clinical Oncology.
Vaccinating patients who have glioblastoma multiforme (GBM) with dendritic cells and either acid-eluted peptides or an antigen-specific peptide has shown promising results in extending patient survival. Likewise, temozolomide (Temodar) has been shown to prolong survival in these patients and has become part of a standard treatment regimen.
However, temozolomide also often induces a profound and long-lasting lymphopenia that could limit immunotherapeutic approaches, such as vaccination.
“This preliminary experience suggests that sequential administration of chemotherapy and immunotherapy may not be deleterious,” wrote Dr. John H. Sampson, who is an associate professor of surgery at Duke University in Durham, N.C., and his colleagues.
This analysis involved patients from two ongoing trials, who are newly diagnosed with GBM, are epidermal growth factor receptor variant III (EGFRvIII)-positive, and have had complete resection.
In the ACTIVATE trial, patients received radiation (approximately 60 Gy) and concurrent temozolomide (50–75 mg/m
Peripheral blood counts were monitored in patients. Grade 2 lymphopenia (less than 800 lymphocytes per mcL of blood) was induced in all patients receiving temozolomide after the first cycle. Grade 3 lymphopenia (less than 500 lymphocytes per mcL of blood) was induced in 70% of patients after the first cycle of temozolomide. However, lymphocyte counts returned to normal after treatment with the drug was stopped.
Regulatory T cells increased from 5% to 12% after the combination of temozolomide and radiation. Cycles of temozolomide do not appear to have diminished EGFRvIII-specific CD3-positive/CD8-positive T cells producing interferon-gamma. EGFRvIII-specific IgG responses were induced and maintained during temozolomide.
Dr. Sampson did not report having any relevant conflicts of interest.