General Information

Tecvayli (teclistamab-cqyv) is a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager.

Tecvayli is specifically indicated for the treatment of 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. 

Tecvaylu is supplied as an injection for subcutaneous administration. The recommended dosing schedule for Tecvayli is provided below.

• The recommended dosage of Tecvayli is step-up doses of 0.06 mg/kg and 0.3 mg/kg followed by 1.5 mg/kg once weekly until disease progression or unacceptable toxicity.
• Administer pretreatment medications (Corticosteroid, Histamine-1 (H1) receptor antagonist, Antipyretics) prior to each dose of the Tecvayli step-up dosing schedule, which includes step-up dose 1, step-up dose 2, and the first treatment dose as described below.
• Administer Tecvayli subcutaneously according to the step-up dosing schedule below to reduce the incidence and severity of cytokine release syndrome (CRS). Due to the risk of CRS and neurologic toxicity, including ICANS, patients should be hospitalized for 48 hours after administration of all doses within the Tecvayli step-up dosing schedule.

• See drug label for recommendations on restarting Tecvayli after dose delays. 
• Step-up dose 2 may be given between 2 to 4 days after step-up dose 1 and may be given up to 7 days after step-up dose 1 to allow for resolution of adverse reactions.
• First treatment dose may be given between 2 to 4 days after step-up dose 2 and may be given up to 7 days after step-up dose 2 to allow for resolution of adverse reactions.

Mechanism of Action

Tecvayli is a first-in-class, bispecific T-cell engager antibody that is administered as a subcutaneous treatment. This off-the-shelf therapy is designed to activate the immune system by binding to the CD3 receptor expressed on the surface of T-cells and to the B-cell maturation antigen (BCMA) expressed on the surface of multiple myeloma cells and some healthy B-lineage cells.

Side Effects

Adverse effects associated with the use of Tecvayli may include, but are not limited to, the following:

• pyrexia
• cytokine release syndrome
• musculoskeletal pain
• injection site reaction
• fatigue
• upper respiratory tract infection
• nausea
• headache
• pneumonia
• diarrhea

The most common Grade 3 to 4 laboratory abnormalities (≥20%) are decreased lymphocytes, decreased neutrophils, decreased white blood cells, decreased hemoglobin, and decreased platelets

The Tecvayli drug label includes a boxed warning for Cytokine Release Syndrome (CRS) and Neurologic Toxicity including immune effector cell-associated neurotoxicity syndrome in addition to warnings and precautions for hepatotoxicity, infections, neutropenia, hypersensitivity and other administrative reactions and embryo-fetal toxicity.

Clinical Trial Results

This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

The FDA’s accelerated approval decision was based on the phase 2 MajesTEC-1 clinical trial which included patients who had received a median of five prior lines of therapy (n=110). An overall response rate (ORR) of 61.8% was achieved, notably with 28.2% of patients achieving a complete response (CR) or better (CR or stringent complete response [sCR]). The median time to first response was 1.2 months. With a median follow-up of 7.4 months, the estimated duration of response (DOR) rate was 90.6% at six months and 66.5% at nine months. The study included heavily pretreated patients, and 78 percent of patients received four or more prior lines of therapy. All patients were triple-class exposed and 76 percent were triple-class refractory (to a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody).