Adoptive immunotherapy with antigen-specific T cells in myeloma: a model of tumor-specific donor lymphocyte infusion

Abstract 

Although partial remissions rates of up to 60% are obtained with conventional therapeutic regimens, multiple myeloma is essentially an incurable disease with a median survival of approximately 30 months. Allogeneic stem cell transplantation (SCT) results in a high percentage of complete remissions (CRs), but it can be associated with significant treatment-related mortality. Recent clinical studies have shown that highly immunosuppressive, yet nonmyeloablative, doses of fludarabine-based chemotherapy can result in alloengraftment. However, even with a reduction in treatment-related mortality, success with allogeneic SCT is limited by the significant risk of relapse. The goal of the strategy described is to transfer tumor antigen-specific immunity induced in the stem cell donor to the allogeneic SCT recipient to reduce relapse. Donors are immunized with a well-defined vaccine, specific for the patient’s tumor. The allogeneic SCT is performed with a conditioning regimen consisting of cyclophosphamide and fludarabine, and the stem cell source is blood mobilized with filgrastim, which could potentially enhance the transfer of a larger number of tumor-specific T cells in the allograft, as compared to bone marrow. Donor immunization with myeloma idiotype protein in the setting of a nonmyeloablative SCT may represent a novel strategy for the treatment of myeloma.