title: Immune-related Adverse Events of Dendritic Cell Vaccination Correlate With Immunologic and Clinical Outcome in Stage III and IV Melanoma Patients.
abstract: The purpose of this study was to determine the toxicity profile of dendritic cell (DC) vaccination in stage III and IV melanoma patients, and to evaluate whether there is a correlation between side effects and immunologic and clinical outcome. This is a retrospective analysis of 82 stage III and 137 stage IV melanoma patients, vaccinated with monocyte-derived or naturally circulating autologous DCs loaded with tumor-associated antigens gp100 and tyrosinase. Median follow-up time was 54.3 months in stage III patients and 12.9 months in stage IV patients. Treatment-related adverse events occurred in 84% of patients; grade 3 toxicity was present in 3% of patients. Most common adverse events were flu-like symptoms (67%) and injection site reactions (50%), and both correlated with the presence of tetramer-positive CD8 T cells (both P<0.001). In stage III melanoma patients experiencing flu-like symptoms, median overall survival (OS) was not reached versus 32.3 months in patients without flu-like symptoms (P=0.009); median OS in patients with an injection site reaction was not reached versus 53.7 months in patients without an injection site reaction (P<0.05). In stage IV melanoma patients (primary uveal and mucosal melanomas excluded), median OS in patients with or without flu-like symptoms was 13.1 versus 8.9 months, respectively (P=0.03); median OS in patients with an injection site reaction was 15.7 months versus 9.8 months in patients without an injection site reaction (P=0.003). In conclusion, DC vaccination is safe and tolerable and the occurrence of the immune-related side effects, such as flu-like symptoms and injection site reactions, correlates with immunologic and clinical outcome.
authors.affiliation: Departments of *Medical Oncology †Tumor Immunology ‡Radiology and Nuclear Medicine, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen §Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Steve
authors.initials: S
authors.lastname: Boudewijns
authors.forename: Harm
authors.initials: H
authors.lastname: Westdorp
authors.forename: Rutger H T
authors.initials: RH
authors.lastname: Koornstra
authors.forename: Erik H J G
authors.initials: EH
authors.lastname: Aarntzen
authors.forename: Gerty
authors.initials: G
authors.lastname: Schreibelt
authors.forename: Jeroen H A
authors.initials: JH
authors.lastname: Creemers
authors.forename: Cornelis J A
authors.initials: CJ
authors.lastname: Punt
authors.forename: Carl G
authors.initials: CG
authors.lastname: Figdor
authors.forename: I Jolanda M
authors.initials: IJ
authors.lastname: de Vries
authors.forename: Winald R
authors.initials: WR
authors.lastname: Gerritsen
authors.forename: Kalijn F
authors.initials: KF
authors.lastname: Bol
mesh_terms: D000328:Adult; D000368:Aged; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D064789:Immunity, Heterologous; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000378:metabolism; D009367:Neoplasm Staging; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D014611:Vaccination; D055815:Young Adult; D058951:gp100 Melanoma Antigen / Q000378:metabolism
chemical_list: D019496:Cancer Vaccines; D058951:gp100 Melanoma Antigen; D014442:Monophenol Monooxygenase