Teclistamab
Overview
Teclistamab is a bispecific monoclonal antibody designed to bind simultaneously to the CD3 receptor on T lymphocytes and to B-cell maturation antigen expressed on malignant plasma cells in multiple myeloma. By engaging both targets, teclistamab brings cytotoxic T cells into close proximity with myeloma cells, resulting in T-cell activation, cytokine release, and targeted tumor cell killing. This immune-redirecting mechanism allows the patient’s own immune system to directly eliminate cancer cells independent of traditional antigen presentation pathways. Teclistamab represents an advanced form of immunotherapy developed for patients with advanced multiple myeloma who have exhausted standard treatment options. It is administered by subcutaneous injection and is designed for long-term disease control in the relapsed or refractory setting. The molecule plays a significant role in modern myeloma management by addressing resistance to prior therapies and offering an immune-based therapeutic strategy.
Background and Date of Approval
Teclistamab was developed as a first-in-class bispecific antibody targeting BCMA and CD3 for the treatment of multiple myeloma. The United States Food and Drug Administration granted accelerated approval to teclistamab on October 25, 2022 for adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. The approval was based on results from the MajesTEC-1 clinical trial, which demonstrated meaningful and durable responses in heavily pretreated patients. The European Medicines Agency granted conditional marketing authorization in August 2022 for a similar indication, recognizing the unmet clinical need in this patient population. These approvals established teclistamab as a novel immune-engaging therapy in multiple myeloma.
Uses
Teclistamab is indicated as monotherapy for adult patients with relapsed or refractory multiple myeloma who have received multiple prior therapies, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. It is used in patients with advanced disease where standard therapeutic options are no longer effective. Teclistamab is not currently approved for first-line use and is reserved for later-line treatment in specialized oncology settings.
Administration
Teclistamab is administered via subcutaneous injection using a step-up dosing schedule designed to reduce the risk of immune-mediated toxicities. Initial doses are given at lower levels, followed by escalation to a standard maintenance dose of 1.5 mg per kilogram administered once weekly. In patients who achieve and maintain a deep response for a defined duration, dosing frequency may be reduced to once every two weeks under approved protocols. Treatment is continued until disease progression or unacceptable toxicity. Regular clinical and laboratory monitoring is required throughout therapy.
Side Effects
Common side effects associated with teclistamab include cytokine release syndrome, fatigue, infections of the upper respiratory tract, injection site reactions, nausea, diarrhea, headache, and musculoskeletal pain. Hematologic abnormalities such as neutropenia, lymphopenia, anemia, and thrombocytopenia are frequently observed. The severity and frequency of these effects vary among patients and are generally manageable with appropriate monitoring and supportive care.
Warnings
Serious adverse events related to teclistamab include severe or life-threatening cytokine release syndrome and neurologic toxicities, including immune effector cell-associated neurotoxicity syndrome. Patients are also at increased risk of serious infections, prolonged cytopenias, and hypersensitivity reactions. Due to these risks, treatment interruption or permanent discontinuation may be required in severe cases. Pregnancy risk should be assessed prior to treatment initiation, as immune-modulating therapies may pose potential harm to the fetus.
Precautions
Baseline evaluation before starting teclistamab includes complete blood counts, assessment for active infections, and evaluation of organ function. Close monitoring is required during treatment for early detection of immune-related toxicities and hematologic abnormalities. Caution is advised in patients with pre-existing immunosuppression or significant comorbidities. Live vaccines should generally be avoided during therapy. Clinically significant drug interactions are uncommon, but additive immunosuppressive effects may occur when used with other immune-modulating agents.
Expert Tips
Appropriate patient selection is critical and should confirm prior treatment exposure and refractory disease status. Step-up dosing protocols must be followed carefully, with patient education focused on early symptom recognition of cytokine release syndrome and neurologic events. Baseline and ongoing laboratory monitoring should be coordinated with clinical assessments. Pharmacists should ensure proper storage, handling, and administration practices and reinforce adherence to monitoring and follow-up schedules to optimize safety and efficacy.