Immunotherapy Combination for Advanced Multiple Myeloma
The FDA has approved teclistamab with daratumumab hyaluronidase-fihj for certain patients with pretreated multiple myeloma.
The U.S. Food and Drug Administration (FDA) approved teclistamab (Tecvayli) in combination with daratumumab hyaluronidase-fihj (Darzalex Faspro) for adult patients with relapsed or refractory multiple myeloma that has been treated with one or more prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent.
The FDA also converted a 2022 accelerated approval to a full approval for teclistamab as a monotherapy for patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy that included a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.
Teclistamab is a bispecific T-cell engager, a type of T cell-redirecting immunotherapy that uses a two-headed antibody to connect a patient’s own T cells with cancer cells. Teclistamab simultaneously binds the CD3 receptor present on T cells and the B-cell maturation antigen (BCMA) that is highly expressed on the surface of multiple myeloma cells. As a result, T cells are activated to kill cancer cells.
Daratumumab hyaluronidase-fihj is an immunotherapy that combines a monoclonal antibody (daratumumab) and the hyaluronidase-fihj enzyme. The monoclonal antibody targets the protein CD38, which is highly expressed on the surface of multiple myeloma cells, resulting in cancer cell death, while the hyaluronidase component partially breaks down the extracellular matrix so that daratumumab can reach CD38-expressing cells more effectively.
The 2022 accelerated approval made teclistamab the first BCMA-targeting bispecific T-cell engager to be approved for any cancer and the first bispecific T-cell engager approved for multiple myeloma. The newly approved combination regimen allows teclistamab to be used in earlier lines of treatment.
The approval of teclistamab plus daratumumab hyaluronidase-fihj was based on results from MajesTEC-3, a randomized, open-label, multicenter trial in which 587 patients with relapsed or refractory multiple myeloma were randomly assigned (1:1) to the teclistamab and daratumumab hyaluronidase-fihj combination arm or the control treatment arm. Individuals in the control arm received the investigator’s choice of either daratumumab hyaluronidase-fihj, pomalidomide, and dexamethasone or daratumumab hyaluronidase-fihj, bortezomib, and dexamethasone.
Median progression-free survival (PFS) was not reached in the teclistamab and daratumumab hyaluronidase-fihj arm and was 18.1 months in the control arm, translating to an 83% reduction in the risk of disease progression or death for patients in the teclistamab and daratumumab hyaluronidase-fihj arm compared with those in the control arm. In addition, teclistamab and daratumumab hyaluronidase-fihj treatment was associated with a 54% reduction in the overall risk of death.
The prescribing information for teclistamab includes a boxed warning for life-threatening or fatal toxicities, including cytokine release syndrome (CRS) and neurologic toxicity. CRS is caused by the rapid release of cytokines into the blood and presents with symptoms like fever, nausea, headache, rash, and rapid heartbeat. Neurologic toxicity includes immune effector cell-associated neurotoxicity syndrome (ICANS), which may be associated with increased cytokine levels in the brain and disruption of the blood-brain barrier.
Multiple myeloma is a form of blood cancer in which abnormal plasma cells located in the bone marrow grow out of control and form tumors in the bones. The National Cancer Institute estimated that 36,110 individuals would be diagnosed with multiple myeloma, and 12,030 patients would die of the disease in the United States in 2025.
The FDA rendered its decision on March 5, 2026. Check this resource for updated information on all therapeutics regulated by the FDA.