Severe adverse immunologic reaction in a patient with glioblastoma receiving autologous dendritic cell vaccines combined with GM-CSF and dose-intensified temozolomide.
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.
UF Brain Tumor Immunotherapy Program, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Department of Neurosurgery, University of Florida, Gainesville, Florida. duane.mitcehell@neurosurgery.ufl.edu john.sampson@duke.edu.
Duane A
DA
Mitchell
UF Brain Tumor Immunotherapy Program, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Department of Neurosurgery, University of Florida, Gainesville, Florida.
Elias J
EJ
Sayour
Duke Brain Tumor Immunotherapy Program, Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina.
Elizabeth
E
Reap
Duke Brain Tumor Immunotherapy Program, Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina.
Robert
R
Schmittling
UF Brain Tumor Immunotherapy Program, Preston A. Wells, Jr. Center for Brain Tumor Therapy, Department of Neurosurgery, University of Florida, Gainesville, Florida.
Gabriel
G
DeLeon
Duke Brain Tumor Immunotherapy Program, Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina.
Pamela
P
Norberg
Duke Brain Tumor Immunotherapy Program, Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina.
Annick
A
Desjardins
Duke Brain Tumor Immunotherapy Program, Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina.
Allan H
AH
Friedman
Duke Brain Tumor Immunotherapy Program, Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina.
Henry S
HS
Friedman
Duke Brain Tumor Immunotherapy Program, Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina.
Gary
G
Archer
Duke Brain Tumor Immunotherapy Program, Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina. duane.mitcehell@neurosurgery.ufl.edu john.sampson@duke.edu.
John H
JH
Sampson
D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects*; D001323:Autoantibodies / Q000096:biosynthesis; D019496:Cancer Vaccines / Q000009:adverse effects* / Q000627:therapeutic use; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives*; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D005909:Glioblastoma / Q000276:immunology / Q000628:therapy*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000009:adverse effects* / Q000276:immunology / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077204:Temozolomide
D018906:Antineoplastic Agents, Alkylating; D001323:Autoantibodies; D019496:Cancer Vaccines; D003606:Dacarbazine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000077204:Temozolomide