Multiple myeloma is a cancer that originates in plasma cells, a type of white blood cell found in the bone marrow. These abnormal plasma cells, known as myeloma cells, can multiply uncontrollably, crowding out healthy blood cells and producing dysfunctional proteins. BiTE, or Bispecific T-cell Engager, therapy represents an innovative approach in the treatment of various cancers, including multiple myeloma. This therapy harnesses the body’s own immune system to target and eliminate cancer cells.
Understanding BiTE Therapy
BiTE therapy involves a specialized engineered protein designed to act as a bridge between the body’s immune cells and cancer cells. These synthetic proteins possess two distinct binding sites. One binding site specifically recognizes and attaches to a protein marker found on the surface of T-cells, which are powerful immune cells capable of destroying abnormal cells. The other binding site is engineered to recognize and bind to a different protein marker located on the surface of cancer cells.
Once a BiTE molecule has bound to both a T-cell and a cancer cell, it effectively brings them into close proximity. This physical connection activates the T-cell, prompting it to release cytotoxic substances directly onto the linked cancer cell. The activated T-cell then initiates a process that leads to the destruction of the cancer cell, essentially re-directing the immune system’s attack. This mechanism allows T-cells to identify and eliminate cancer cells they might not otherwise recognize as a threat, enhancing the body’s natural defenses against malignancy.
BiTE Therapy’s Application in Myeloma
BiTE therapy is applied in multiple myeloma by targeting proteins highly expressed on the surface of myeloma cells. A prominent target for BiTE drugs in multiple myeloma is B-cell maturation antigen (BCMA). This protein is found predominantly on the surface of malignant plasma cells and is rarely present on healthy cells, making it an ideal target for precise therapy.
By binding to BCMA on myeloma cells and to CD3 on T-cells, BiTE molecules like teclistamab (an FDA-approved therapy) and elranatamab facilitate the T-cell-mediated killing of cancerous cells. These therapies are designed to specifically engage the immune system to recognize and eliminate myeloma cells while minimizing harm to healthy tissues.
Administration and Management of Side Effects
BiTE therapies for multiple myeloma are administered through injections, with some given intravenously and others subcutaneously. Some, like teclistamab, follow an initial “step-up” dosing schedule, where smaller doses are given before the full treatment dose to help manage potential side effects. The specific dosing schedule and frequency depend on the particular BiTE drug and the patient’s individual response.
A notable side effect associated with BiTE therapy is cytokine release syndrome (CRS), which can manifest with symptoms such as fever, chills, fatigue, and muscle aches. Neurological toxicities, including confusion, headaches, or tremors, can also occur. These side effects arise from the widespread activation of T-cells and the subsequent release of inflammatory proteins called cytokines. Management of CRS often involves supportive care, such as fever reduction, and in more severe cases, medications like tocilizumab, which blocks a key cytokine involved in CRS. Close monitoring for both CRS and neurological symptoms is standard practice, particularly during the initial treatment cycles, to ensure prompt intervention.
Patient Eligibility and Treatment Landscape
Patient eligibility for BiTE therapy in multiple myeloma focuses on individuals whose disease has either returned (relapsed) or has not responded to previous therapies (refractory) after receiving multiple prior treatments. This includes patients who have exhausted common treatment options.
BiTE therapy is positioned within the broader treatment landscape of multiple myeloma as an option for patients with advanced disease. It offers a new mechanism of action for patients who may no longer respond to conventional chemotherapy, immunomodulators, or proteasome inhibitors. While not a first-line therapy, BiTEs provide a therapeutic avenue for individuals with a challenging form of the disease. These therapies expand the range of available treatments for patients whose multiple myeloma has become difficult to control.