A vaccine targeted at 3 antigens showed promising results in a phase 1 study of patients with multiple myeloma (MM). The study results were recently reported in the journal Blood Advances.
The vaccine is a messenger RNA (mRNA)-based vaccine using autologous Langerhans-type dendritic cells (LCs) that had been electroporated with mRNA for CT7, MAGE-A3, and WT1 genes. It was aimed at targeting residual disease in patients with MM following autologous stem cell transplantation (ASCT).
The phase 1 trial (ClinicalTrials.gov Identifier: NCT01995708) enrolled patients in a treatment arm who received the vaccine in a priming dose 12 days after ASCT, with booster doses given at 30 and 90 days following ASCT. A control group consisted of patients who underwent ASCT and supportive care but without receiving the vaccine. Both groups received lenalidomide maintenance therapy beginning 3 months after ASCT. The vaccine consisted of 9×106 patient-derived LCs, which had been combined from 3×106 LCs each that had been electroporated with mRNA from each of the 3 genes. The goal of the study was to assess safety, toxicity, and immunogenicity with this vaccine.
A total of 34 patients were prescreened, of whom 97% showed positivity for 1 or more of the 3 antigens targeted by the vaccine. Among randomized patients, 10 were placed in the treatment arm, and 10 patients were in the control arm. After induction and prior to ASCT, each group had 9 patients in very good partial response and 1 in complete response.
When analyzed at 1 and 3 months following the final vaccination, patients who received the vaccine showed evidence of elevated antigen-specific CD4 T-cell secretion of the cytokines interferon g, interleukin-2, and tumor necrosis factor-a; at 3 months these cytokines were present at 5.69-, 5.32-, and 2.54-fold higher levels, respectively, than before vaccination. Antigen-specific CD8 T-cell secretion of these cytokines also was similarly elevated.
Patients who received the vaccine reportedly developed local reactions with the booster doses that were considered mild, with no adverse events above grade 1. The most common adverse events were erythema, induration, and mild pruritus associated with the injection site, and these were most notable after the final vaccine dose.
The study investigators considered the results of this study to demonstrate safety and feasibility with this vaccination approach in this patient population. “This study highlights the feasibility of immunizing MM patients with mRNA-electroporated LCs after ASCT to induce measurable cellular immune responses against multiple antigens simultaneously,” the study investigators concluded in their report.
Chung D, Sharma S, Rangesa M, et al. Langerhans dendritic cell vaccines bearing mRNA-encoded tumor antigens induce anti-myeloma immunity after autotransplant. Blood Adv. Published online January 31, 2022. doi:10.1182/bloodadvances.2021005941