Vaccination with Dendritic Cell/Tumor Fusions following Autologous Stem Cell Transplant Induces Immunologic and Clinical Responses in Multiple Myeloma Patients

Abstract

Background A multiple myeloma (MM) vaccine has been developed whereby patient derived tumor cells are fused with autologous dendritic cells (DCs), creating a hybridoma that stimulates a broad anti-tumor response. We report on the results of a phase II trial in which patients underwent vaccination following autologous stem cell transplantation (ASCT) to target minimal residual disease. Methods Twenty-four patients received serial vaccinations with DC/myeloma fusion cells following post-transplant hematopoietic recovery. A second cohort of 12 patients received a pre-transplant vaccine followed by post-transplant vaccinations. DCs generated from adherent mononuclear cells cultured with GM-CSF, IL-4 and TNFα were fused with autologous bone marrow-derived MM cells using polyethylene glycol (PEG). Fusion cells were quantified by determining the percentage of cells that co-express DC and MM antigens. Findings The post-transplant period was associated with reduction in general measures of cellular immunity; however, an increase in CD4 and CD8+ myeloma specific T cells was observed after ASCT that was significantly expanded following post-transplant vaccination. Seventy-eight percent of patients achieved a best response of CR+VGPR and 47% achieved a CR/nCR. Remarkably, 24% of patients who achieved a partial response following transplant were converted to CR/nCR after vaccination and at over 3 months post-transplant, consistent with a vaccine-mediated effect on residual disease. Interpretation The post-transplant period for patients with multiple myeloma provides a unique platform for cellular immunotherapy in which vaccination with DC/MM fusions resulted in the marked expansion of myeloma specific T cells and cytoreduction of minimal residual disease.

Beyond consolidation: auto-SCT and immunotherapy for plasma cell myeloma

“…A larger series of a total of 26 patients had similar results, 59 and other Id-based strategies are under investigation. 60 Rosenblatt et al 61 used DC/PCM cell fusions in the early postauto-HCT setting as additional consolidation. Vaccination resulted in the expansion of myeloma-reactive lymphocytes and expansion of T cells with specificity for myeloma-associated Ags such as MUC1.…”

Cellular immunotherapy in multiple myeloma: Lessons from preclinical models

“…In another phase II clinical trial, minimal residual disease was targeted in myeloma patients after auto-SCT using DC/tumor fusion vaccines. The results were encouraging, as DC/tumor fusion vaccination during the post-transplantation period resulted in an expansion of myelomaspecific T cells and a reduction of minimal residual disease [144].…”

Preclinical and clinical evaluation of elotuzumab, a SLAMF7-targeted humanized monoclonal antibody in development for multiple myeloma

“…Thus, there is an urgent unmet medical need for more effective therapies. Other potential treatment approaches that could be utilized in multiple myeloma to overcome immune deficiencies include therapeutic vaccines [74,75], and chimeric antigen receptor-expressing T cells [76,77]; although further investigations are still needed with these agents. Immune dysfunction is a key characteristic of multiple myeloma and, therefore, directly targeting and stimulating the immune system is promising treatment of approach.…”