title: Patient-specific vaccines derived from autologous tumor cell lines as active specific immunotherapy: results of exploratory phase I/II trials in patients with metastatic melanoma.
abstract: Seventy-four (74) patients with metastatic melanoma were treated with patient-specific vaccines derived from autologous tumor cell lines. Cryopreserved irradiated tumor cells were injected weekly for 3 weeks, then monthly for 5 months. At a median follow up >6 years, the median event-free survival (EFS) was 4.5 months, with 13 patients alive and progression free 6-12 years later. Median overall survival (OS) was 20.5 months, with 29% 5-year OS. Tumor response rate was 9% among the 35 patients with evaluable disease who received at least 3 injections. Better survival was observed for patients who had minimal rather than clinically evident metastatic disease at the time vaccine therapy was initiated (5-yr OS 47% vs. 13%; p < 0.0001), received granulocyte-macrophage colony-stimulating factor and/or interferon gamma as an adjuvant (5-yr EFS 26% vs. 0%; p < 0.0001) or received an average of <7 million cells for each of the first 3 injections, compared to those who received 7-11.9 million or >12 million cells per injection (5-yr EFS OS 35% vs. 24%; p = 0.041 and p = 0.034). There was a trend toward better EFS for those who had a positive delayed type hypersensitivity (DTH) reaction to an intradermal injection of 1 million irradiated tumor cells at baseline, or converted to positive after 3 injections, compared to those whose DTH remained negative (5-yr EFS 39% vs. 18%; p = 0.159). This treatment approach is feasible, produces minimal toxicity, and is associated with longterm survival in a significant proportion of patients.
authors.affiliation: Hoag Cancer Center, Newport Beach, CA 92658, USA. rdillman@hoaghospital.org
authors.forename: Robert O
authors.initials: RO
authors.lastname: Dillman
authors.forename: Carol
authors.initials: C
authors.lastname: DePriest
authors.forename: Cristina
authors.initials: C
authors.lastname: DeLeon
authors.forename: Neil M
authors.initials: NM
authors.lastname: Barth
authors.forename: Lee S
authors.initials: LS
authors.lastname: Schwartzberg
authors.forename: Linda D
authors.initials: LD
authors.lastname: Beutel
authors.forename: Patric M
authors.initials: PM
authors.lastname: Schiltz
authors.forename: Shankar K
authors.initials: SK
authors.lastname: Nayak
mesh_terms: D019496:Cancer Vaccines / Q000627:therapeutic use* / Q000633:toxicity*; D045744:Cell Line, Tumor; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D009682:Magnetic Resonance Spectroscopy; D008545:Melanoma / Q000000981:diagnostic imaging / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D009362:Neoplasm Metastasis / Q000276:immunology; D018579:Patient Selection; D012189:Retrospective Studies; D016019:Survival Analysis; D017741:Survivors; D014057:Tomography, X-Ray Computed
chemical_list: D019496:Cancer Vaccines