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Blood and Marrow Transplant Clinical Trials Network - A Phase II Multicenter Trial of Single Autologous Hematopoietic Cell Transplant Followed by Lenalidomide Maintenance for Multiple Myeloma with or without Vaccination with Dendritic Cell/Myeloma Fusions (BMT CTN-1401-BioLINCC)

Data Access NOTE: Please refer to the "Authorized Access" section below for information about how access to the data from this accession differs from many other dbGaP accessions.

Objectives: To compare response at one year post transplant between participants receiving dendritic cell/myeloma vaccine along with granulocyte macrophage colony-stimulating factor (GM-CSF) and lenalidomide maintenance therapy to those receiving lenalidomide maintenance therapy with or without GM-CSF.

Background: The advent of combination biologic therapy for multiple myeloma (MM) has significantly improved patient outcomes. Induction therapy followed by consolidation with autologous hematopoietic stem cell transplantation (auto-HCT) prolongs progression-free survival in patients with MM. The addition of post-transplant lenalidomide maintenance therapy further extends the duration of remission. However, the vast majority of patients ultimately experience disease progression due to the emergence of resistant disease. The development of strategies to enhance the durability of post-transplant response remains a major unmet need in the field. Since MM is associated with immune suppression, the development of cancer vaccines is being investigated in MM with the goal of stimulating tumor-specific immunity. Dendritic cells (DC) are the most potent antigen-presenting cells that prominently express costimulatory signaling necessary for optimal T-cell activation, cross-presentation of antigen to reactive CD8 T cells, and the development of primary immunity. The BMT CTN developed a personalized cancer vaccine in which patient-derived tumor cells are fused with autologous monocyte-derived DCs. The BMT CTN-1401 study examined the efficacy of the DC/MM fusion vaccine in conjunction with lenalidomide maintenance therapy after auto-HCT, compared with maintenance alone.

Participants: Participants with symptomatic MM were eligible if they were 18-70 years old, were candidates for auto-HCT, had a Karnofsky Performance status of ≥70%, had >20% plasma cells in the bone marrow aspirate differential <60 days prior to enrollment, had received <1 cycle of systemic anti-myeloma therapy, and had a creatine clearance of ≥ 40mL/min. Exclusion criteria included individuals with active autoimmune disease or prior auto or allo transplant.

A total of 140 participants were randomized. 68 participants were randomized to the vaccine arm, 37 to the lenalidomide plus GM-CSF arm, and 35 to the lenalidomide alone arm.

Design: BMT CTN-1401 was a phase II, multicenter, open label trial. All participants underwent bone marrow aspiration following enrollment. Myeloma cells were isolated, preserved, and for participants randomized to the vaccine arm, used for vaccine generation. All participants received standard-of-care induction therapy and auto-HCT conditioned with melphalan. Participants were randomized approximately 2 months post-transplant. Participants were randomized in a 2:1:1 ratio to the vaccine arm (DC/MM vaccine, GM-CSF, plus lenalidomide), or one of two control arms (lenalidomide plus GM-CSF or lenalidomide alone). All participants began maintenance lenalidomide between day 90 and 100 post-transplant at a dose of 10 mg a day for 28 days of a 28-day cycle. On day 1 of cycles 2, 3, and 4 of lenalidomide maintenance, patients assigned to the vaccine arm underwent subcutaneous administration of the DC/MM fusion vaccine along with 100 μg GM-CSF administered subcutaneously adjacent to the vaccine site on days 1 to 4. Participants randomized to the control arms received either lenalidomide alone or lenalidomide with GM-CSF at the same dose and schedule as the vaccine arm.

The primary outcome was a comparison of participants in complete response (CR)/stringent CR (sCR) at 1-year post-transplant between the vaccine and control arms. The primary immunologic endpoint of the study was a comparison of the percentage of circulating multiple myeloma–reactive T cells between participants in the vaccine and control arms. PFS (progression-free survival) and OS (overall survival) were secondary endpoints of the study.

Conclusions: There was not a statistically significant difference in the percentage of participants achieving complete response 1-year post-transplant in the vaccine arm compared to the control arms.