The US Food and Drug Administration (FDA) has approved Tecvayli (teclistamab-cqyv) plus Darzalex Faspro (daratumumab and hyaluronidase-fihj) for the treatment of adults with relapsed or refractory multiple myeloma (R/R MM) who have received at least one prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent.
MM is a form of cancer that occurs due to abnormal and uncontrolled growth of plasma cells in the bone marrow. When present, the most common symptom is anemia, which can be associated with fatigue and shortness of breath. Other features of the condition may include multiple infections, abnormal bleeding, bone pain, weak and/or easily broken bones, and numbness and/or weakness of the arms and legs. The exact underlying cause of disease is currently unknown. Factors that are associated with an increased risk of developing MM include increasing age, male sex, African American race, radiation exposure, a family history of the condition, obesity, and/or a personal history of monoclonal gammopathy of undetermined significance (MGUS).
Teclistamab is a first-in-class, bispecific T-cell engager antibody therapy designed to activate the immune system by binding to the CD3 receptor and B-cell maturation antigen (BCMA). It was approved in 2022 as a subcutaneous treatment for adult patients with R/R MM who have received at least four prior lines of therapy. Daratumumab and hyaluronidase is a subcutaneous CD38-directed antibody co-formulated with recombinant human hyaluronidase that received FDA approval in 2020 and is approved for 11 indications in MM. The combination therapy works together to prime and activate the immune system to eradicate myeloma cells that express the BCMA protein.
The approval is supported by data from the MajesTEC-3 clinical trial, an ongoing, phase 3, randomized, study evaluating the safety and efficacy of teclistamab plus daratumumab versus choice of daratumumab and dexamethasone with either pomalidomide or bortezomib in patients with R/R MM.
The combination therapy demonstrated statistically significant improvements in progression-free survival (83% compared to 30% in the control arm) and overall survival compared to standard treatment after a follow-up of three years. Results also showed an 83% reduction in the risk of disease progression or death compared to standard treatment regimens. Significant improvements were also observed in treatment response rates, minimal residual disease (MRD)-negativity, overall survival, and time to worsening of symptoms.
Teclistamab plus daratumumab and hyaluronidase showed higher overall response rates (89% versus 75.3%), complete response (81.8% versus 32.1%), and MRD-negativity (58.4% versus 17.1%) at three years of follow-up.
Teclistamab plus daratumumab and hyaluronidase and standard of care had similar rates of Grade 3/4 treatment-emergent adverse events (TEAE). Most Grade 3/4 events were due to cytopenias and infection. Cytokine release syndrome occurred in 60.1% of patients. All cases were Grade 1/2, did not lead to treatment discontinuation and were effectively managed. Immune effector cell-associated neurotoxicity syndrome occurred in 1.1% of patients. Serious adverse events occurred in 70.7% of patients compared to 62.4% of patients treated with the control regimen, while treatment discontinuations due to adverse events were low (4.6% vs. 5.5%).
The teclistamab MajesTEC-3 supplemental Biologics License Application (sBLA) was selected in the Commissioner’s National Priority Voucher (CNPV) Pilot Program. The program seeks to expedite approval of applications that address critical national health priorities, such as bringing innovative therapies to the American people, addressing large unmet medical needs, promoting domestic manufacturing, and increasing affordability. A company selected for the program is issued a voucher entitling the company to benefits including enhanced communications and rolling review to allow for a shortened review time.
For more information, visit the press release.
To learn more about MM and other rare cancers, visit https://checkrare.com/diseases/cancers/
