Partial T Cell-Depleted Allogeneic Stem Cell Transplantation following Reduced-Intensity Conditioning Creates a Platform for Immunotherapy with Donor Lymphocyte Infusion and Recipient Dendritic Cell Vaccination in Multiple Myeloma

Flow chart of the tandem autologous SCT followed by RIC-SCT and posttransplantation cellular immunotherapy.

Clinical course of patient UPN2 (A) and patient UPN17 (B). The Y-axis on the left shows disease load as measured by serum FLCs or M-protein, and is shown with the green line. The Y-axis on the right shows the percentage recipient cells in peripheral blood and is shown with a purple line. Triangle in blue indicates autologous SCT, triangle in red indicates RIC-SCT, triangle in orange indicates DLI, and triple-triangle in blue indicates 1 cycle of DC-vaccinations.

(A) Preclinical study of characteristics of mature DC generated from cryopreserved apheresis products from 4MM patients. Apheresis was performed after autologous SCT. Cultured DC had a mature phenotype with high expression of CD83, CD80, and CD86. (B) In vitro stimulation capacity of mature DC generated from cryopreserved apheresis products. DC from patients 1 and 2 and patients 3 and 4 were tested with responder cells from different healthy donors.

(A) Characteristics of DC vaccine from thawed apheresis products. Postcryopreservation, the yield of PBMC varied from 45% to 90% and yield of CD14⁺ monocytes varied from 25% to 57%. Yield of mature DC from CD14⁺ cells was sufficient in 4 patients (9%-16%); however, <5% in 2 patients. Viability of the vaccination product was >90% for all administered vaccines. (B) DC vaccine phenotype. All administered DC vaccines had a mature phenotype with high expression of the cell surface antigens CD83, CD80, CD86, and CCR7.

(A) KLH specific T cell proliferation indicated as stimulation index. (B) Regulatory T cells (CD25 bright+ cells within the CD3⁺CD4⁺ population) before and after each DC vaccination in 5 patients treated with DC vaccination.

Clinical course of patient UPN3 (A) and patient UPN7 (B). The Y-axis on the left shows disease load as measured by serum FLCs or M-protein, and is shown with the green line. The Y-axis on the right shows the percentage recipient cells in peripheral blood and is shown with a purple line. Triangle in blue indicates autologous SCT, triangle in red indicates RIC-SCT, triangle in orange indicates DLI, and triple-triangle in blue indicates 1 cycle of DC vaccinations.

Clinical course of patient UPN8. The Y-axis on the left shows disease load as measured by serum FLCs or M-protein, and is shown with the green line. The Y-axis on the right shows the percentage recipient cells in PB and is shown with a purple line. Triangle in blue indicates autologous SCT, triangle in red indicates RIC-SCT, triangle in orange indicate DLI and triple-triangle in blue indicate 1 cycle of DC vaccinations.

OS of 20 patients after RIC-SCT with a median follow-up of 27 months. (A) Current PFS of 20 patients after RIC-SCT. Progression was noted when systemic therapy was started.