Multiple myeloma is a blood cancer originating in plasma cells, a type of white blood cell found in the bone marrow. These abnormal plasma cells multiply uncontrollably, producing dysfunctional proteins and displacing healthy blood cells. Bispecific antibodies represent an advancement in treating this disease, offering a new approach to harness the body’s immune system against cancer.
Understanding Bispecific Antibodies
Bispecific antibodies are engineered proteins designed to bind to two different targets simultaneously. For multiple myeloma, one arm attaches to a marker on myeloma cells, while the other binds to a receptor on the patient’s immune T-cells. This dual binding brings T-cells into close proximity with myeloma cells.
This interaction allows T-cells to recognize and attack cancerous plasma cells more effectively. By linking immune cells to tumor cells, bispecific antibodies facilitate a targeted immune response, leading to the destruction of malignant cells.
FDA-Approved Bispecific Antibodies for Multiple Myeloma
Several bispecific antibodies have received U.S. Food and Drug Administration (FDA) approval for treating multiple myeloma. These therapies are primarily for patients with relapsed or refractory disease who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.
Teclistamab (Tecvayli) was the first T-cell redirecting bispecific antibody approved by the FDA for multiple myeloma. It received accelerated approval in 2022. This therapy targets the CD3 receptor on T-cells and the B-cell maturation antigen (BCMA) on multiple myeloma cells.
Elranatamab (Elrexfio) gained accelerated FDA approval in 2023. Like teclistamab, elranatamab targets BCMA on myeloma cells and CD3 on T-cells.
Talquetamab (Talvey) received accelerated FDA approval in 2023. This bispecific antibody uniquely targets GPRC5D, a protein found on multiple myeloma cells, in addition to the CD3 receptor on T-cells.
Linvoseltamab-gcpt (Lynozyfic) received accelerated FDA approval in 2025. This bispecific antibody targets BCMA on myeloma cells and CD3 on T-cells.
Patient Considerations and Treatment Management
Patients receiving bispecific antibody therapy for multiple myeloma require close monitoring due to potential side effects. A common side effect is cytokine release syndrome (CRS), which can manifest as fever, fatigue, chills, and muscle aches. CRS occurs when activated immune cells release inflammatory proteins. Mild cases are managed with supportive care; severe cases may require medications to suppress the immune response.
Another potential side effect is immune effector cell-associated neurotoxicity syndrome (ICANS), which can affect the nervous system. Symptoms of ICANS may include confusion, difficulty speaking, or tremors. Both CRS and ICANS are reversible with prompt management.
Administration of bispecific antibodies involves an initial hospitalization period. This allows close observation during the “step-up dosing” phase, where patients receive gradually increasing doses. This approach helps mitigate initial side effects like CRS. Subsequent doses can often be administered outpatient, but monitoring remains important.
Looking Ahead: The Evolving Landscape
Research into bispecific antibodies for multiple myeloma is rapidly advancing, exploring new therapeutic avenues. Scientists are investigating new bispecific antibodies targeting different myeloma cell proteins to expand treatment options. These agents are also being studied in combination with other therapies to enhance effectiveness.
Clinical trials are underway to evaluate the potential of bispecific antibodies in earlier lines of therapy for multiple myeloma. This could shift their use to earlier in the disease course. The development of these therapies holds promise for improving outcomes and quality of life for individuals with multiple myeloma.