Allogeneic dendritic cell (DC) vaccination as an “off the shelf” treatment to prevent or delay relapse in elderly acute myeloid leukemia patients: Results of phase I study.

3029 Background: Vaccines against tumor-associated antigens represent an appealing strategy for preventing tumor recurrence. A novel immunotherapy platform is represented by the DCOne cell line, which originates from a human myeloid leukemia cell line, endogenously expresses a range of tumor associated antigens and can be differentiated into mature dendritic cells. Methods: A phase I study enrolled 12 AML patients (age range 58-71) who were either in CR1/CR2 (n=5) or had smouldering disease (n=7), at high risk of relapse and ineligible for available post-remission therapies, in a 3+3 design, starting with 4 bi-weekly intradermal DCOne DC vaccinations of 10E6 cells (n=3), 25E6 (n=3) or 50E6 (n=6). Patients were monitored for clinical and immunological responses for 126 days and surviving patients were followed up after study completion. Results: Treatment was well tolerated in all patients, with expected toxicities of injection site reactions (< grade 2). During the study 3 patients died: 2 from infections and 1 from leukemia. Patients who survived more than 6 months post-vaccination showed remarkable survival (22 mo after the first patient was recruited, 3 patients have been alive for 22, 20 and 16 months respectively). One patient with smouldering AML at entry achieved CR2 after vaccination; one patient who was in CR2 at entry, relapsed 8 mo after vaccination and entered CR3 following a single low dose of 5-AZA. Remarkably, 1/5 patients that were evaluable by IFNg ELIPOTs showed vaccination-induced specific T cell responses to WT-1 and PRAME, antigens present in DCOne DC. In addition, increased post vaccination delayed type hypersensitivity reactions were observed in all cohorts. Furthermore, induction of systemic immune responses, with increases in CD4+ and CD8+ T cell proliferative responses and/or seroconversion to DCOne DC and/or AML blasts was seen in 5 out of 9 patients. Conclusions: Vaccination with DCOne derived DC is feasible in AML, generated cellular and humoral immune responses, and interesting clinical responses. The hypothesis that immune responses correlate with clinical benefit will be investigated in a randomised phase II trial. Clinical trial information: NCT01373515.