Patient-Specific Dendritic Cell Vaccines with Autologous Tumor Antigens in 72 Patients with Metastatic Melanoma

Abstract

Aim: Metastatic melanoma patients were treated with patient-specific vaccines consisting of autologous dendritic cells loaded with antigens from irradiated cells from short-term autologous tumor cell lines. Patients & methods: A total of 72 patients were enrolled in a single-arm Phase I/II (NCT00948480) trial or a randomized Phase II (NCT00436930). Results: Toxicity was minimal. Median overall survival (OS) was 49.4 months; 5-year OS 46%. A 5-year OS was 72% for 18 recurrent stage 3 without measurable disease when treated and 53% for 30 stage 4 without measurable disease when treated. A total of 24 patients with measurable stage 4 when treated (median of four prior therapies) had an 18.5 months median OS and 46% 2-year OS. Conclusion: This dendritic cell vaccine was associated with encouraging survival in all three clinical subsets. Clinicaltrial.gov NCT00436930 and NCT00948480.

Survival Comparison between Melanoma Patients Treated with Patient-Specific Dendritic Cell Vaccines and Other Immunotherapies Based on Extent of Disease at the Time of Treatment

“…All patients provided written informed consent prior to treatment. Details regarding these trials and the 72-DCV-treated patients were previously published [16][17][18][19].…”

“…Two of the major differences between these trials and most cancer vaccine trials is that the starting point for the preparation of the vaccine was surgical resection of tumor, and a short-term cell line had to be established as the source of ATA. Patients were typically referred for possible vaccine because they had surgically-resectable regionally recurrent stage 3 or distant stage 4 oligometastatic disease, or they were undergoing resection of a metastatic lesion for diagnostic or palliative reasons [19]. It was often several months later before the autologous cell line was available, and/or the patient was referred by their managing physician for treatment.…”

“…It was often several months later before the autologous cell line was available, and/or the patient was referred by their managing physician for treatment. As a result, in the interval from tumor collection to referral for treatment, many patients experienced recurrence and/or progression of disease, while others remained disease free, or they were rendered free of measurable metastatic disease by stereotactic radiation to the brain or resection of new metastases, or in rare cases by combination chemotherapy and biotherapy [19]. Survival varied depending on patients' disease status at the time DC-ATA was initiated.…”

“…Survival varied depending on patients' disease status at the time DC-ATA was initiated. The survival curves for each of these cohorts and their clinical characteristics were recently published [19]. Patients whose most advanced stage of melanoma was recurrent stage 3 and had no measurable disease at the time of DC-ATA treatment had a 72% survival rate at five years; patients whose most advanced stage of melanoma was stage 4, but had no measurable disease at the time of DC-ATA treatment had a 53% five-year survival; patients with measurable stage 4 disease had a median survival of 18.5 months and a two-year survival of 46% [19].…”

“…The survival curves for each of these cohorts and their clinical characteristics were recently published [19]. Patients whose most advanced stage of melanoma was recurrent stage 3 and had no measurable disease at the time of DC-ATA treatment had a 72% survival rate at five years; patients whose most advanced stage of melanoma was stage 4, but had no measurable disease at the time of DC-ATA treatment had a 53% five-year survival; patients with measurable stage 4 disease had a median survival of 18.5 months and a two-year survival of 46% [19]. In the current study, efforts were made to identify comparable control groups from the literature for the purpose of survival comparisons between patients that were treated with DC-ATA and patients treated with other forms of immunotherapy.…”