Dendritic cell vaccination loaded with tumor cell antigens in multiple myeloma

Multiple myeloma (MM) is a disease that has not provided a long term complete cure, despite use of new drugs and high response rates with autologous stem cell transplantation (autoSCT). Complete response is obtained with the effects of graft versus myeloma (GVM) in MM treatment with allogeneic stem cell transplantation (alloSCT) and donor lymphocyte infusion (DLI). However, allo-reactive response is not specific and high mortality and morbidity rates are observed due to the graft-versus-host disease (GVHD). Therefore, therapeutic investigations are focused on treatment alternatives providing specific immune response in MM. Though cancer vaccines eliminate minimal residual disease in MM by stimulating tumor-specific T cells and decreasing tolerance of T cells, it is not sufficiently reflected to result of treatment. In the study, we designed to evaluate the efficacy and safety of dendritic cell (DC) cancer vaccine pulsed with tumor antigen in MM patients.For this purpose, 27 patients diagnosed with MM were enrolled in the study. After appropriate treatment, autoSCT was performed in all patients. DC cancer vaccine was administered to 10 patients, thalidomide treatment was provided to 7 patients. 10 patients were followed-up without any treatment. Following autoSCT, in DC cancer vaccine group very good partial response (VGPR) was obtained in 6 of the patients while partial response (PR) was found in 4 patients, in patients receiving thalidomide treatment VGPR was determined in 4 patients while PR was seen in 3 patients and in patients without any treatment VGPR was found in 6 patients and PR was seen in 4 patients. In addition, after autoSCT, improvement to VGPR was observed after administration of DC cancer vaccine in 2 patients with PR. Response to treatment, time to disease progression and treatment-related side effects were evaluated in all patients. At the end of follow-up period of 2 years, progression of disease was observed in approximately 8 months in 3 patients in DC cancer vaccine group while the corresponding time of disease progression in other cases were determined as 7, 9, 11, 14, 15 and 23 months, respectively; no progression of disease was found in 1 patient in 42th week of follow up. On the other hand, progression of disease was found in 3rd month in 2 patients who received thalidomide after autoSCT while the corresponding time of disease progression was detected as 7 and 18th months in other patients; no disease progression was found in 1 patient during a follow-up period of 28 months. Among patients with no additional treatment following autoSCT, progression of disease was found during 2-7 months after autoSCT in 4 patients with PR and within 3-13 months in 6 patients with VGPR. Assessment of time to disease progression after autoSCT showed a duration of 15 months in patients who received DC cancer vaccine, 12 months in patients treated with thalidomide and 6 months in patients followed up without any further treatment. While time to disease progression after autoSCT were longer in DC cancer vaccine and thalidomide groups, difference was statistically insignificant; however, in untreated patients was significantly shorter than DC cancer vaccine group (p<0.05). Treatment-associated side effects were observed in all patients treated with thalidomide, leading to stop of treatment in 2 patients. On the other hand, side effects in DC cancer vaccine group were transient and tolerable while no stop of treatment was observed in any of the patients.In conclusion, DC cancer vaccine was demonstrated to be safe and effective as a maintenance treatment following autoSCT in MM cases and it is suggest that utilization of new cytokines and adjuvants in formulation of cancer vaccine and reduction of T regulatory cells (Treg) will be able to provide more improvement in efficacy.