Poster Session II: Gene therapy, cellular immunotherapy and vaccination - Clinical
Recent data from the National Cancer Institute showed that 50% of myeloma patients survive after 5 years which is encouraging but also warns the international myeloma community that there is an unmet need for improvement. Dendritic cells have been used in clinical trials as cellular mediators for therapeutic vaccination in patients with cancer. There are two main trends: the implementation of next generation dendritic cell vaccines that have improved immunogenicity, and the emerging paradigm of combination of dendritic cell vaccination with other cancer therapies.
The Dendritic Cell Myeloma Project In Antwerp is part of a set of clinical trials for diseases with Unmet Medical needs like acute myeloid leukemia, mesothelioma, glioblastoma and multiple sclerosis. The presented study was performed between 2010 and 2013 while we were analyzing our pilot study of autologous dendritic cell vaccination therapy in acute myeloid leukemia and before the accessibility in Belgium of monoclonal antibody therapies against CD38 and SLAMF7 and Chimeric Antigen Receptor T (CAR T) Cell Therapy directed against BCMA.
We vaccinated 8 myeloma patients. Some had high risk cytogenetics others not. Median age was 55 year making it the patient group the most in need for better and stronger therapies. After leukapheresis, CD14 selection and 6 days of culturing we uploaded them with the WT1 antigen. Vaccination with 10 million DC's was done in the outpatient clinic by intradermal injections near the axillary lymph nodes. Vaccines were given on a 2-weekly base with a minimum of four. To monitor hematological responses bone marrow biopsies were taken before and after 4 vaccinations. For Immune monitoring we performed a delayed type hypersensitivity test after 4 vaccinations.
We could give a median number of 12 vaccinations. Delayed type hypersensitivity test was positive in all 8 cases. International Myeloma Working Group Responses after 4 vaccinations show a persistent stable disease in 4 patients, a persistent stringent complete response in one patient and a conversion from a complete response into a stringent complete response in 3 patients. Median overall survival is 10.5 years (with a minimum of 5 years and a maximum of 13 years. 3 patients are still alive. Median overall survival after vaccination start is 4.5 years.
An induction of dendritic cell vaccine specific T cell immune responses was seen in all patients and 5 year overall survival is 100%. With a vaccine production of one week and with total costs of 25.000 euro, dendritic cell vaccines are socio-economic affordable treatment options compared with other immunotherapies. An important issue will be the timing of the vaccination in the whole treatment scheme especially in the new era of CAR-T cell Therapy.
Acknowledgments: Belgian and Flemish Organizations against Cancer and Fund for Scientific Research Flanders