The European Commission ( EC ) has granted conditional marketing authorisation ( CMA ) of Tecvayli ( Teclistamab ) as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma ( RRMM ).
Patients must have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody and have demonstrated disease progression on the last therapy.
Teclistamab is a first-in-class bispecific antibody that redirects CD3-positive T-cells to B-cell maturation antigen ( BCMA )-expressing myeloma cells to induce the killing of tumour cells.
Multiple myeloma remains an incurable blood cancer, with nearly all patients relapsing and requiring subsequent therapy.
As the disease progresses, relapses for patients become more aggressive with each new line of therapy, and remissions become progressively shorter.
The approval of Teclistamab followed an accelerated approval pathway, supported via the EMA’s PRIME scheme.
The CMA was supported by positive results from the multicohort, open-label phase 1/2 MajesTEC-1 study, evaluating the safety and efficacy of Teclistamab in adults with RRMM ( n =165 ).
Patients received a weekly subcutaneous injection of Teclistamab at a dose of 1.5 mg/kg, after receiving step-up doses of 0.06 mg/kg and 0.3 mg/kg.
In the study, 104 out of 165 patients achieved an overall response rate ( ORR ) of 63% ( 95% Confidence Interval [ CI ]; range, 55.2–70.4 ) after a median of five prior lines of therapy.
Notably, 58.8% of patients receiving Teclistamab has achieved a very good partial response ( VGPR ) or better and 39.4% has achieved a complete response ( CR ) or better.
The median time to the first confirmed response was 1.2 months ( range, 0.2–5.5 months ) and the median duration of response was 18.4 months ( 95% CI; range, 14.9–not estimable ).
Results from the MajesTEC-1 study were also published in The New England Journal of Medicine and have shown that treatment with Teclistamab resulted in deep and durable responses.
The median duration of progression-free survival was 11.3 months ( 95% CI; range, 8.8–17.1 ) and the median duration of overall survival was 18.3 months ( 95% CI; range, 15.1–not estimable ).
Adverse events were consistent with this patient population. The most common adverse effects were cytokine release syndrome ( 72%; 0.6% grade 3, no grade 4 ), neutropenia ( 71%; 64% grade 3 or 4 ) and anaemia ( 55%; 37% grade 3 or 4 ).
Infections were frequent with the most common being upper respiratory tract infections ( 37%; 2.4% grade 3 or 4 ) and pneumonia ( 28%; 19% grade 3 or 4 ).
Hypogammaglobinaemia occurred in 123 patients ( 75% ) and 39% of patients received intravenous or subcutaneous immunoglobulin therapy.
Neurotoxic events were low grade ( 15%; 14% grade 1 or 2 ) and five patients ( 3% ) had immune effector cell-associated neurotoxicity syndrome.
Teclistamab, a bispecific antibody, redirects T-cells through two cellular targets ( BCMA and CD3 ) to activate the body’s immune system to fight the cancer.
Multiple myeloma affects a type of white blood cell called plasma cells, which are found in the bone marrow. In multiple myeloma, cancerous plasma cells change and grow out of control.
In Europe, more than 50,900 people were diagnosed with multiple myeloma in 2020, and more than 32,400 patients died.
While some patients with multiple myeloma initially have no symptoms, others can have common symptoms of the disease which can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels or kidney failure. ( Xagena )
Source: Janssen Pharmaceutical, 2022