What Is Teclistamab?
Teclistamab is an FDA-approved medication for Multiple Myeloma, a type of cancer that affects plasma cells in the bone marrow. It is also being investigated for other related conditions. Teclistamab is a type of immunotherapy known as a bispecific antibody. It works by targeting two specific proteins: B-cell maturation antigen (BCMA) found on myeloma cells, and CD3, which is present on immune cells called T-cells. By binding to both BCMA and CD3, teclistamab brings T-cells close to myeloma cells, helping the T-cells recognize and destroy the cancer cells.
In clinical trials, teclistamab is being studied alone and in combination with other treatments for various forms of multiple myeloma and other blood cancers. The first trial involving teclistamab began on May 9, 2017, and research is ongoing, with the latest trial scheduled to conclude on April 8, 2026. A total of 50 clinical trials have been initiated for teclistamab, enrolling over 10,627 participants to date.
Uses and Conditions Under Study
Teclistamab is primarily under investigation for the treatment of various forms of multiple myeloma and related plasma cell disorders. These conditions are characterized by the abnormal growth of plasma cells in the bone marrow.
- Multiple Myeloma and Related Conditions: Teclistamab is extensively studied for its role in treating multiple myeloma, including relapsed, refractory, and recurrent forms of the disease. These terms describe myeloma that has returned or has not responded to previous treatments. It is also being investigated for high-risk smoldering multiple myeloma, an early stage of the disease. In total, 42 trials are exploring teclistamab for these specific types of multiple myeloma. As a bispecific antibody, teclistamab helps the body's immune system target and eliminate these cancerous plasma cells.
- AL Amyloidosis: This condition involves the buildup of abnormal proteins (amyloid) produced by plasma cells, which can damage organs. Teclistamab is being studied in 5 trials for AL amyloidosis, as it may help reduce the abnormal plasma cells responsible for amyloid production.
- Hematological Malignancies: This is a broad category of cancers affecting the blood, bone marrow, and lymph nodes. Teclistamab is being evaluated in 2 trials for its potential to treat these types of cancers, leveraging its immune-targeting mechanism.
- Higher-risk Myelodysplastic Syndrome (MDS): MDS is a group of disorders where the bone marrow produces immature blood cells that don't mature properly. One trial is studying teclistamab for higher-risk MDS, exploring if it can help improve blood cell production or reduce progression to acute leukemia.
- Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS): This is a neurological side effect that can occur with certain immunotherapies. One trial is investigating ICANS in the context of teclistamab, likely to understand its safety profile or potential management strategies.
Dosing
Teclistamab is administered as an injection, specifically through subcutaneous (SC) and intravenous (IV) routes, as studied in clinical trials. The exact dosage strengths are not specified in the available data, but trials investigate both standard dose and reduced dose regimens of teclistamab, often in combination with other anticancer agents.
Many studies explore teclistamab as part of complex treatment regimens. These include combinations with other drugs such as daratumumab, lenalidomide, pomalidomide, bortezomib, carfilzomib, and dexamethasone. Some trials compare standard-frequency treatment with reduced-frequency bispecific antibody treatments, including teclistamab, for patients with relapsed/refractory multiple myeloma. Other studies examine the use of teclistamab in specific sequences, such as induction, consolidation, and maintenance phases of treatment. For example, some regimens involve teclistamab with daratumumab and lenalidomide (Tec-DR), or teclistamab with lenalidomide (Tec-Len).
Investigational dosing also includes studies on pre-medication, such as the use of siltuximab prior to teclistamab infusion, to assess safety and feasibility. Various cohorts within trials are designed to evaluate different combinations and sequences of teclistamab with other therapies to determine optimal treatment strategies.
Side Effects
In clinical studies, the most common side effects observed in patients taking Teclistamab for relapsed or refractory multiple myeloma were reported from an open-label trial (NCT04557098), meaning there was no placebo group for comparison. These side effects were:
- Cytokine Release Syndrome (CRS), which occurred in 72% of patients. Most cases were mild (Grade 1: 50%, Grade 2: 21%), with severe cases (Grade 3) in 1% of patients.
- Neutropenia (low white blood cell count) in 71% of patients, with 69% experiencing Grade 3 or 4 severity.
- Anemia (low red blood cell count) in 55% of patients, with 40% experiencing Grade 3 or 4 severity.
- Thrombocytopenia (low platelet count) in 49% of patients, with 31% experiencing Grade 3 or 4 severity.
- Fatigue in 46% of patients.
- Upper respiratory tract infections in 37% of patients.
- Nausea in 37% of patients.
- Diarrhea in 36% of patients.
- Pyrexia (fever) in 36% of patients.
Other notable side effects included pneumonia (23%), hypogammaglobulinemia (22%), and neurotoxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), which occurred in 15% of patients, with 1% experiencing Grade 3 severity.
Clinical Trial Results
Teclistamab for Relapsed/Refractory Multiple Myeloma
The effectiveness of Teclistamab was evaluated in the MajesTEC-1 study (NCT04557098), an open-label, single-arm clinical trial involving 165 patients with relapsed or refractory multiple myeloma. All patients had received at least three prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.
The primary measure of effectiveness was the Overall Response Rate (ORR), which indicates the percentage of patients whose cancer responded to treatment. In this study, 63% of patients treated with Teclistamab achieved an overall response. This means 104 out of 165 patients saw a reduction in their cancer.
Further analysis of responses showed:
- Complete Response (CR) or better: 39.4% of patients (65 out of 165) achieved a complete response or better, meaning no detectable signs of cancer or a stringent complete response.
- Very Good Partial Response (VGPR) or better: 58.8% of patients (97 out of 165) achieved a very good partial response or better, indicating a significant reduction in cancer.
Patients typically experienced their first response to treatment within a median of 1.2 months.
Key secondary outcomes provided further insight into the duration of response and survival:
- The median Duration of Response (DoR), which is the length of time that the treatment remained effective, was 18.4 months.
- The median Progression-Free Survival (PFS), which measures the time patients lived without their disease getting worse, was 11.3 months.
- The median Overall Survival (OS), which is the length of time patients lived after starting treatment, was 18.3 months.
These results indicate that Teclistamab can lead to meaningful responses and survival benefits in patients with heavily pretreated relapsed or refractory multiple myeloma.
Currently Recruiting Trials
For patients and caregivers interested in clinical research, several studies are actively recruiting participants to further explore the potential of Teclistamab, a bispecific antibody. These trials investigate Teclistamab both as a standalone treatment and in combination with other therapies for various forms of multiple myeloma and AL amyloidosis.
- A Phase 3 study, NCT07258511, is comparing JNJ-79635322 with an anti-BCMAxCD3 bispecific antibody in 400 participants with relapsed or refractory multiple myeloma.
- The Phase 2 study NCT07107529 is evaluating daratumumab with Teclistamab or Talquetamab for frail, newly diagnosed multiple myeloma patients, targeting 150 individuals.
- For AL amyloidosis, Phase 2 study NCT07110844 investigates the Teclistamab-Daratumumab combination in 25 participants.
- Phase 2 study NCT