The Food and Drug Administration ( FDA ) has granted accelerated approval to Tecvayli ( Teclistamab;Teclistamab-cqyv ), the first bispecific B-cell maturation antigen ( BCMA )-directed CD3 T-cell engager, for 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.
Teclistamab was evaluated in MajesTEC-1, a single-arm, multi-cohort, open-label, multi-center study.
The efficacy population consisted of 110 patients who had previously received at least 3 prior therapies, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, and had not received prior BCMA-targeted therapy.
The main efficacy outcome measure was overall response rate ( ORR ) as determined by the Independent Review Committee assessment using International Myeloma Working Group 2016 criteria.
ORR was 61.8% ( 95% CI: 52.1, 70.9 ).
With a median follow-up of 7.4 months among responders, the estimated duration of response ( DOR ) rate was 90.6% ( 95% CI: 80.3%, 95.7% ) at 6 months and 66.5% ( 95% CI: 38.8%, 83.9% ) at 9 months.
The prescribing information for Tecvayli has a Boxed Warning for life threatening or fatal cytokine release syndrome ( CRS ) and neurologic toxicity, including immune effector cell-associated neurotoxicity ( ICANS ).
Among patients who received Teclistamab at the recommended dose, CRS occurred in 72% of patients, neurologic toxicity in 57%, and ICANS in 6%.
Grade 3 cytokine release syndrome occurred in 0.6% of patients and grade 3 or 4 neurologic toxicity occurred in 2.4%.
Because of the risks of cytokine release syndrome and neurologic toxicity, including ICANS, Teclistamab is available only through a restricted program under a Risk Evaluation and Mitigation Strategy ( REMS ), called the Tecvayli REMS.
The most common adverse reactions ( 20% or more ) occurring in the 165 patients in the safety population, were pyrexia, cytokine release syndrome, musculoskeletal pain, injection site reaction, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, and diarrhea.
The most common grade 3 to 4 laboratory abnormalities ( 20% or more ) were decreased lymphocytes, decreased neutrophils, decreased white blood cells, decreased hemoglobin, and decreased platelets.
The recommended Teclistamab dose is 0.06 mg/kg via subcutaneous injection on day 1, 0.3 mg/kg on day 4, and 1.5 mg/kg on day 7, followed by 1.5 mg/kg once weekly until disease progression or unacceptable toxicity. ( Xagena )
Source: FDA, 2022