Teclistamab

Teclistamab is a bispecific T-cell–engaging antibody used to treat certain adults with relapsed or refractory multiple myeloma, a cancer of plasma cells in the bone marrow. It binds to two targets: B-cell maturation antigen (BCMA), which is expressed on myeloma cells, and CD3, a protein found on T cells of the immune system. By bringing T cells into close contact with BCMA-expressing cancer cells, teclistamab activates immune cells to attack and destroy the malignant cells. It is administered by subcutaneous injection and requires a carefully supervised starting schedule with gradually increasing doses, known as step-up dosing, to reduce the risk of serious immune reactions. Depending on the approved indication and jurisdiction, teclistamab may be used alone after multiple previous treatments or in combination with daratumumab in eligible patients whose disease has returned or failed to respond to prior therapy. Important risks include cytokine release syndrome, neurological toxicity, low blood-cell counts and serious infections. Treatment therefore requires specialist oversight, preventive measures and regular laboratory monitoring. Teclistamab can provide meaningful disease control in appropriately selected patients, but it does not guarantee remission or cure multiple myeloma, and the cancer may eventually become resistant to treatment.

Teclistamab is a bispecific antibody developed to redirect T cells against BCMA-expressing multiple myeloma cells. Its clinical development included the MajesTEC-1 phase 1/2 study, which evaluated teclistamab in heavily pretreated patients with relapsed or refractory disease. The United States Food and Drug Administration (FDA) granted accelerated approval for monotherapy on 25 October 2022 for adults who had received at least four previous lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody. On 5 March 2026, the FDA converted the monotherapy indication to traditional approval and approved teclistamab in combination with daratumumab and hyaluronidase for eligible adults who had received at least one previous line of therapy, including a proteasome inhibitor and an immunomodulatory agent. The combination approval was supported by the phase 3 MajesTEC-3 trial. In the European Union, the European Medicines Agency (EMA) authorised Tecvayli on 23 August 2022, initially under conditional marketing authorisation, for eligible adults with relapsed or refractory multiple myeloma after at least three previous therapies. The EU authorisation was converted to standard marketing authorisation on 20 August 2026, and the authorised indication includes combination treatment with daratumumab for eligible adults after at least one prior therapy. Approval criteria and dosing should be confirmed against the current local product information.

Teclistamab is used to treat adults with relapsed or refractory multiple myeloma, meaning the cancer has returned after treatment or has not responded adequately. As monotherapy, it is indicated for appropriately pretreated patients whose disease has progressed following multiple prior therapies, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody. In the United States, this indication requires at least four prior lines of therapy; the European indication specifies at least three prior therapies. Teclistamab is also approved in combination with daratumumab and hyaluronidase in eligible adults who have received at least one prior line of therapy including a proteasome inhibitor and an immunomodulatory agent, subject to the applicable local label. Combination treatment uses complementary mechanisms to target myeloma. Treatment selection depends on prior medicines, disease characteristics, general health, infection risk and local authorisation requirements.

Teclistamab is administered by subcutaneous injection under the supervision of a healthcare team experienced in treating multiple myeloma. The dose is calculated according to body weight, and treatment begins with a step-up dosing schedule using gradually increasing doses before the recommended maintenance dose. For monotherapy, the usual maintenance schedule is once weekly; dosing every two weeks may be considered for eligible patients who have maintained a sufficiently deep response for the required period, according to the applicable prescribing information. When used with daratumumab and hyaluronidase, teclistamab follows a combination-specific step-up schedule and maintenance intervals that become less frequent as treatment progresses. Premedication is given to reduce the risk of cytokine release syndrome. Under the current US prescribing information, patients require hospitalisation for 48 hours after each of the first two step-up doses, with further monitoring instructions for the first treatment dose. Treatment generally continues until disease progression or unacceptable toxicity. Exact doses, timing, premedication and observation requirements must follow the current local product label.

Common side effects of teclistamab include cytokine release syndrome, low levels of immunoglobulins, upper respiratory tract infections, pneumonia, fever, fatigue, headache, cough, diarrhoea, nausea, muscle or bone pain and reactions at the injection site. Abnormal blood counts are also common, including reduced neutrophils, red blood cells, platelets and lymphocytes. Low potassium levels may occur. In combination with daratumumab and hyaluronidase, reported adverse effects also include COVID-19, decreased body weight and other infections. The type and severity of side effects vary among patients and may be influenced by prior treatments and the underlying disease. Some effects can be managed with supportive care, dose delays or treatment adjustments under medical supervision. Patients should report fever, new respiratory symptoms, unusual bruising, bleeding or persistent weakness promptly.

Teclistamab carries boxed warnings in the United States for potentially life-threatening or fatal cytokine release syndrome (CRS) and neurological toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS). CRS may cause fever, low blood pressure, rapid heartbeat or breathing difficulties, while neurological toxicity can present as confusion, reduced alertness, difficulty speaking, tremors or seizures. Serious or fatal infections, severe neutropenia, hypogammaglobulinemia and liver toxicity are also important risks. Severe complications may require hospital treatment, interruption of therapy or permanent discontinuation depending on their nature and severity. The medicine is subject to a restricted risk-management programme in the United States. Step-up dosing, premedication and close observation are essential during treatment initiation. Patients should seek urgent medical assessment for fever, breathing difficulty, confusion, severe headache, reduced consciousness or other rapidly worsening symptoms. Treatment decisions should be made by the treating oncology team.

Before treatment, clinicians should assess the patient's blood counts, liver function, infection status and overall clinical condition. Immunoglobulin levels should be evaluated and monitored because teclistamab can cause substantial antibody deficiency and increase susceptibility to infection. Active infections should be assessed and managed, and antiviral, antibacterial or other preventive measures may be appropriate according to the patient's risk and local guidance. Vaccination status should be reviewed; live vaccines should be avoided during treatment and until immune recovery, as specified by the relevant product information. Patients should discuss pregnancy, contraception and breastfeeding with their oncology team because fetal risk and the effects on breastfeeding are not fully established. Formal drug-interaction data are limited, but concomitant medicines that suppress immunity or increase infection risk require careful review. Patients should inform clinicians about all prescription medicines, non-prescription products and supplements. Renal or hepatic impairment, frailty and previous treatment-related complications may require additional clinical assessment and monitoring.

Confirm the patient's diagnosis, prior treatment history and eligibility against the locally approved indication before starting teclistamab. Explain the step-up dosing schedule and ensure that premedication, observation and required hospitalisation are arranged before the first doses. Educate patients and caregivers about CRS, ICANS and infection symptoms, including fever, confusion, difficulty speaking, severe headache and breathing problems, and provide clear instructions on when to seek emergency care. Assess complete blood counts, liver function, immunoglobulin levels and infection risk at baseline and throughout treatment. Coordinate preventive care, including infection prophylaxis and immunoglobulin replacement when clinically indicated. Review vaccination plans and concomitant immunosuppressive medicines. Pharmacists should verify the prescribed weight-based dose, product strength, preparation requirements and administration schedule. Patients should be advised to keep scheduled appointments, report new symptoms promptly and avoid driving or hazardous activities if neurological symptoms or treatment-related impairment occurs. Ongoing care should be coordinated with the haematology team and other specialists as needed.