Data from Randomized Trial of a Personalized Dendritic Cell Vaccine after Autologous Stem Cell Transplant for Multiple Myeloma

Abstract Purpose: Vaccination with dendritic cell (DC)/multiple myeloma (MM) fusions has been shown to induce the expansion of circulating MM-reactive lymphocytes and consolidation of clinical response following autologous hematopoietic cell transplant (autoHCT). Patients and Methods: In this randomized phase II trial (NCT02728102), we assessed the effect of DC/MM fusion vaccination, GM-CSF, and lenalidomide maintenance as compared to control arms of GM-CSF and lenalidomide or lenalidomide maintenance alone on clinical response rates and induction of MM-specific immunity at 1-year post-transplant. Results: The study enrolled 203 patients, with 140 randomized post-transplantation. Vaccine production was successful in 63/68 patients. At 1 year, rates of CR were 52.9% (vaccine) and 50% (control) (p=0.37, 80% CI 44.5%, 61.3% and 41.6%, 58.4%, respectively), and rates of VGPR or better were 85.3% (vaccine) and 77.8% (control) (p=0.2). Conversion to CR at 1 year was 34.8% (vaccine) and 27.3% (control) (p=0.4). Vaccination induced a statistically significant expansion of MM-reactive T cells at 1 year as compared to prior to vaccination (p=0.024) and in contrast to the non-vaccine arm (p=0.026). Single-cell transcriptomics revealed clonotypic expansion of activated CD8 cells and shared dominant clonotypes between patients at 1-year post-transplant. Conclusions: DC/MM fusion vaccination with lenalidomide did not result in a statistically significant increase in CR rates at 1-year post-transplant but was associated with a significant increase in circulating MM-reactive lymphocytes indicative of tumor-specific immunity. Site-specific production of a personalized cell therapy with centralized product characterization was effectively accomplished in the context of a multicenter cooperative group study.