Teclistamab, MOA, Dosing, Protocol, NCCP, and Side Effects

Teclistamab:

• What is Teclistamab?
• MOA
• Dosing
• Protocol
• NCCP
• Side Effects

What is Teclistamab?

Teclistamab is a bispecific antibody treatment used for patients with relapsed or refractory multiple myeloma. It is designed to target both the BCMA (B-cell maturation antigen) found on myeloma cells and CD3 receptors on T-cells. By binding to both cell types, teclistamab essentially helps the immune system recognize and attack myeloma cells more effectively. It is typically used after multiple prior lines of therapy have failed, including proteasome inhibitors, immunomodulators, and anti-CD38 antibodies.

Teclistamab is administered as a subcutaneous injection and is part of a newer class of immunotherapies known as bispecific T-cell engagers (BiTEs). Because it activates the immune system, it requires careful monitoring, especially early in treatment. Hospitals often use step-up or ramp-up dosing to reduce the risk of cytokine release syndrome (CRS), one of the common immune-related reactions associated with T-cell–directing therapies.

MOA (Mechanism of Action)

Teclistamab works through a dual-targeting mechanism. One arm of the antibody binds to BCMA on multiple myeloma cells, while the other binds to CD3 receptors on T-cells. This brings T-cells into close proximity with malignant plasma cells. Once engaged, the T-cells become activated and begin to release cytotoxic molecules, which attack and kill the myeloma cells. This immune-mediated killing mechanism bypasses many of the pathways that myeloma cells use to evade standard therapies.

Because it uses the patient’s own immune system, teclistamab does not rely on the typical cancer-killing pathways of chemotherapy. Instead, it unleashes a targeted immune attack. This mechanism has shown strong effectiveness even in heavily pretreated patients, making teclistamab an important therapeutic option for advanced multiple myeloma. However, immune activation also explains the risk of CRS, infections, and neurotoxicity, which require early and ongoing monitoring.

Dosing

Teclistamab uses a step-up dosing schedule to reduce the risk of serious immune reactions. Treatment typically begins with two smaller ramp-up doses given several days apart, followed by a larger first full treatment dose. For example, patients may receive a step-up dose on Day 1, a higher step-up dose on Day 4, and then the full therapeutic dose on Day 7. This staged escalation helps the body adjust to immune activation.

After the initial doses, teclistamab is usually administered weekly via subcutaneous injection. In some treatment protocols, dosing may be extended to every two weeks once the disease is controlled and the patient is stable. Dose adjustments may be needed for severe side effects or in patients who develop infections or organ dysfunction. Healthcare providers follow strict protocols to ensure safe administration.

Protocol

The clinical protocol for teclistamab includes premedication, step-up dosing, monitoring, and supportive care. Before each step-up dose, patients may receive medications such as corticosteroids, antihistamines, and antipyretics to reduce the risk of cytokine release syndrome. During and after dosing, patients are monitored closely for fever, low blood pressure, or breathing difficulty—early signs of immune reactions.

Most protocols require hospitalization or observation during the first few doses for safety. Once the patient tolerates treatment well, further injections may be given in an outpatient setting. Additional protocol components include infection screening, immunoglobulin replacement for hypogammaglobulinemia, and neurologic monitoring for immune effector neurotoxicity syndrome (ICANS). The protocol emphasizes early detection and intervention to prevent complications.

NCCP

The NCCP (National Cancer Control Programme) guidelines provide standardized treatment recommendations for teclistamab. These guidelines outline dosing schedules, monitoring requirements, adverse-event management, and criteria for patient eligibility. They ensure consistent, evidence-based care across oncology centers and help clinicians follow the safest approach for administering the drug.

NCCP documents also detail premedication regimens, criteria for interrupting or reducing doses, and supportive care strategies such as antimicrobial prophylaxis. Because teclistamab significantly suppresses the immune system, NCCP guidelines emphasize infection surveillance and vaccination strategies to protect patients throughout therapy.

Side Effects

Like many immunotherapies, teclistamab can cause several side effects. The most common is cytokine release syndrome (CRS), characterized by fever, fatigue, low blood pressure, and breathing difficulties. CRS typically occurs during the first week of therapy, especially during ramp-up dosing, and is treated with supportive care and medications such as tocilizumab if needed.

Other side effects include infections, due to lowered immune function; neurotoxicity (ICANS) with symptoms such as confusion or tremors; low blood counts including neutropenia and anemia; and hypogammaglobulinemia, which may require IVIG replacement. Injection site reactions, fatigue, and gastrointestinal symptoms are also common. With proper monitoring and early intervention, many side effects can be successfully managed while maintaining treatment effectiveness.