A Study of an Additional Antibody Treatment for Newly Diagnosed Multiple Myeloma Prior to Autologous Stem Cell Transplantation

Multiple myeloma is a malignant disease of the bone marrow in which certain white blood cells (plasma cells) undergo pathological changes and multiply uncontrollably. Healthy plasma cells normally produce antibodies that help the body fight off infections. Genetic changes in these cells play a key role in the development of the disease. If high-dose chemotherapy and a transplant of the patient’s own stem cells (autologous stem cell transplant) are options, newly diagnosed multiple myeloma can be treated with the antibody daratumumab, bortezomib, lenalidomide, and dexamethasone (DVRd). This is followed by high-dose chemotherapy with melphalan, then the reinfusion of the patient’s own blood stem cells that were previously collected, and maintenance therapy. Maintenance therapy serves to preserve the treatment gains achieved so far and prevent relapses. The study drug teclistamab is a bispecific antibody that simultaneously binds to the BCMA marker on myeloma cells and to the body’s own immune cells (T cells), bringing them into close contact so that the T cells can attack the cancer cells. Teclistamab is typically injected under the skin (subcutaneously) and has not yet been approved for the treatment of untreated, newly diagnosed multiple myeloma.

The goal of this Phase 3 study is to investigate whether the addition of teclistamab can increase the proportion of patients with no detectable residual disease before the start of maintenance therapy. Patients will be randomly assigned to one of three treatment groups. Study arm 1 will receive teclistamab with daratumumab, lenalidomide, and dexamethasone (Tec-DRd) for six cycles, followed by high-dose melphalan chemotherapy, an autologous stem cell transplant, and maintenance therapy with daratumumab and lenalidomide. Study arm 2 receives Tec-DRd for six cycles, followed by high-dose chemotherapy with melphalan, an autologous stem cell transplant, and maintenance therapy with daratumumab, lenalidomide, and teclistamab. The control arm receives the DVRd combination for four cycles, followed by high-dose melphalan chemotherapy, an autologous stem cell transplant, two additional cycles of DVRd, and maintenance therapy with daratumumab and lenalidomide. The study is open-label, which means that both the medical staff and the patient know which medications are being administered. The main objective (primary endpoint) of the study is the proportion of patients in whom no myeloma cells are detectable in the bone marrow prior to the start of maintenance therapy using a highly sensitive assay (no detectable residual disease, MRD-negativity). Additional objectives include determining how often this state persists for at least twelve months and how often serious infections or prolonged treatment interruptions occur during the first 24 months of maintenance therapy.

Eligible participants include women and men aged 18 to 70 with newly diagnosed, previously untreated multiple myeloma that requires treatment and for which high-dose therapy with autologous stem cell transplantation is an option. Patients who are ineligible for participation include, among others, those who have previously received BCMA-targeted or T-cell-mediated therapy.