MedicalResearch.com: What are the main findings of the study?
Dr. Dillman: The main finding of this study is that among 149 metastatic melanoma patients treated with high-dose interleukin-2 (IL2), survival was much better in the subset of 32 patients who also were treated with patient-specific vaccines (that is active specific immunotherapy or ASI) that contained antigens from tumor cell lines derived from there own metastases that had been surgically resected. The 5-year survival rate from the date of starting IL2 was 39% in those receiving vaccine compared to 13% in those who did not (p<0.001). A number of studies have reported that a 5-year survival rate of 15% is typical for patients treated with IL2. The data also suggested that 5-year survival was better in the 25 patients who received the vaccine after, rather than before IL2 (46% vs 14%), p<0.001). Among the 32 ASI-treated patients, there was a trend for survival benefit for the 16 patients treated with autologous dendritic cells pulsed with antigens from the autologous melanoma cells and injected with granulocyte-macrophage colony stimulating factor (GM-CSF) compared to injections of irradiated tumor cells with or without GM-CSF (p=0.17)
MedicalResearch.com: Were any of the findings unexpected?
Dr. Dillman: We were testing the null hypothesis that having received such a vaccine had no effect on survival for patients treated with IL2. The results of the study suggest otherwise. Through the years there have been a number of papers suggesting that various immunotherapy treatments may have been interactive whether given concurrently or sequentially. The limitation of this study is that it is retrospective, and the data is not as powerful as that from a randomized trial. There is one randomized trial in metastatic melanoma that compared IL2 to IL2 with a peptide vaccine, which showed a strong trend toward a survival benefit for the addition of the vaccine. There is randomized trial data suggesting that the combination of dendritic cells and irradiated tumor cells injected with GM-CSF is associated with better survival than injections of tumor cells and GM-CSF.
MedicalResearch.com: What should clinicians and patients take away from your report?
Dr. Dillman: Active specific immunotherapy utilizing the antigens from autologous tumor stem cells may be an important adjunctive treatment to other immunotherapy approaches. Additional clinical trials designed to confirm the benefit and safety of this approach in metastatic melanoma are scheduled for the near future. It is important to note that these patient specific products can only be derived from metastatic melanoma; so this is not an option for melanoma prevention, or the treatment of localized melanoma.
For many years IL2 has been a standard treatment, but it is toxic, and in high doses, it has to given in a hospital setting; so it has not been widely embraced by practicing oncologists. There are a lot of exciting therapeutic advances taking place for the treatment of metastatic melanoma, including tyrosine kinase inhibitors that block aberrant intracellular signal transduction, and monoclonal antibodies that inhibit T-lymphocyte checkpoints by blocking a specific receptor or ligand. We can anticipate future randomized trials in which this active specific immunotherapy approach will be tested as an adjunct to these other therapies, especially monoclonal antibodies to T-lymphocyte checkpoint targets such as CTLA-4 and PD1 or its ligand.