Severe adverse immunologic reaction in a patient with glioblastoma receiving autologous dendritic cell vaccines combined with GM-CSF and dose-intensified temozolomide.

Published

Journal Article

Therapeutic vaccination of patients with cancer-targeting tumor-associated antigens is a promising strategy for the specific eradication of invasive malignancies with minimal toxicity to normal tissues. However, as increasingly potent modalities for stimulating immunologic responses are developed for clinical evaluation, the risk of inflammatory and autoimmune toxicities also may be exacerbated. In this report, we describe the induction of a severe (grade 3) immunologic reaction in a patient with newly diagnosed glioblastoma (GBM) receiving autologous RNA-pulsed dendritic cell (DC) vaccines admixed with GM-CSF and administered coordinately with cycles of dose-intensified temozolomide. Shortly after the eighth administration of the admixed intradermal vaccine, the patient experienced dizziness, flushing, conjunctivitis, headache, and the outbreak of a disseminated macular/papular rash and bilateral indurated injection sites. Immunologic workup of patient reactivity revealed sensitization to the GM-CSF component of the vaccine and the production of high levels of anti-GM-CSF autoantibodies during vaccination. Removal of GM-CSF from the DC vaccine allowed continued vaccination without incident. Despite the known lymphodepletive and immunosuppressive effects of temozolomide, these observations demonstrate the capacity for the generation of severe immunologic reactivity in patients with GBM receiving DC-based therapy during adjuvant dose-intensified temozolomide.

Full Text

Duke Authors

Cited Authors

  • Mitchell, DA; Sayour, EJ; Reap, E; Schmittling, R; DeLeon, G; Norberg, P; Desjardins, A; Friedman, AH; Friedman, HS; Archer, G; Sampson, JH

Published Date

  • April 2015

Published In

Volume / Issue

  • 3 / 4

Start / End Page

  • 320 - 325

PubMed ID

  • 25387895

Pubmed Central ID

  • 25387895

Electronic International Standard Serial Number (EISSN)

  • 2326-6074

International Standard Serial Number (ISSN)

  • 2326-6066

Digital Object Identifier (DOI)

  • 10.1158/2326-6066.CIR-14-0100

Language

  • eng