Host Dendritic Cell Vaccinations Combined with Donor Lymphocyte Infusions Induce Host and KLH Specific Immunity in Multiple Myeloma Patients.

Abstract 2875

Poster Board II-851

Allogeneic stem cell transplantation followed by donor lymphocyte infusions (DLI) induces a clinical significant graft versus myeloma (GvM) effect in 30-50% of multiple myeloma (MM) patients. Since this effect can be dependent on the presence of host dendritic cells (DC) at the time of DLI, combining DLI with infusion of host DCs may improve GvM effect. To evaluate this we conducted a phase I/II trial in which DLI- non responding MM patients received host monocyte derived DC vaccinations in combination with a second DLI. Patients received 3 DC vaccinations both i.v. and i.d. with two-week intervals. The first vaccination was combined with DLI. Half of the i.d. DCs was loaded with KLH for immunomonitoring purposes. Specific anti-host and anti-KLH T cell responses were monitored using IFN-gamma release and proliferation assays. To date six patients completed all 3 DC vaccinations, one patient received only one vaccination. Exacerbation of mild pre-existing graft versus host disease occurred in two patients after the first and second vaccination respectively; no other adverse events were seen. Starting from the second vaccination patients developed positive skin reactions against KLH-DCs (n=5/6) and against DCs (n=2/5). The delayed type hypersensivity (DTH) skin tests performed after the last vaccination showed positive indurations against host DCs (n=5/5) and against KLH (n=4/5). All patients (n=4/4) developed significant but variable proliferative and IFN-gamma responses against KLH and host DCs. While 5 patients developed no clinical GvM effect, in one patient disease was stabilized for 29 weeks and the cellular responses against host DCs and KLH were still present 20 weeks after the first vaccination. Another patient, who entered the study with minimal residual disease, is clinically stable for 18 weeks now, however he has not yet been evaluated further. We conclude that administration of host DCs combined with DLI is safe and feasible, and that the vaccinations result in enhanced T cell responses. However, clinical GvM effects are limited. This GvM effect may be increased after vaccination with DCs loaded with hematopoietic restricted minor H antigens.