title: Features associated with survival in metastatic melanoma patients treated with patient-specific dendritic cell vaccines.
abstract: Previously, a 54% 5-year survival was reported for metastatic melanoma patients treated with patient-specific vaccines consisting of autologous dendritic cells loaded with antigens from autologous proliferating tumor cells. This study attempted to determine which clinical and laboratory factors best explained long-term survival in this group of patients. Univariate analyses were used to identify factors associated with continuous survival after initiating vaccine therapy. Multivariate logistic regression was used to identify independent factors to classify survival at 3.5 years. Survivors were followed a minimum of 3.7 years (median: 5.7). Univariate analyses identified eight features associated with improved survival: Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, no measurable disease at study entry, receiving 8 vaccinations, age <50 years, normal baseline lactate dehydrogenase, no history of visceral metastases, anergy to standard skin tests, and failure of interferon-gamma (IFN-γ) to induce apoptosis in autologous tumor cells. After examining 54 variables for which complete information was available over all patients, the best multivariate regression for survival at 3.5 years utilized six features: prior radiation therapy, younger age, male gender, ECOG PS 0, higher numbers of cells administered during the first 3 injections, and lower numbers of viable cells administered during the first 3 injections. This model correctly classified survival for 28 of 32 patients (87%) and death for 20 of 22 (91%). When features with incomplete information were included in the analysis, addition of IFN-γ-induced apoptosis (n=49) improved predictive accuracy to 27 of 29 (93%) for survival and 19 of 20 (95%) for death. Dependencies between variables were common, but these multivariate linear models yielded high classification accuracy for survival at 3.5 years and identified two features of the vaccine itself as being of independent significance.
authors.affiliation: Hoag Cancer Institute; One Hoag Drive, Newport Beach, CA 92658, USA. rdillman@hoaghospital.org
authors.forename: Robert O
authors.initials: RO
authors.lastname: Dillman
authors.forename: Gary B
authors.initials: GB
authors.lastname: Fogel
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Cornforth
authors.forename: Senthamil R
authors.initials: SR
authors.lastname: Selvan
authors.forename: Patric M
authors.initials: PM
authors.lastname: Schiltz
authors.forename: Carol
authors.initials: C
authors.lastname: DePriest
mesh_terms: D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D016015:Logistic Models; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D019496:Cancer Vaccines