On March 5, 2026, the FDA approved teclistamab (Tecvayli) in combination with daratumumab hyaluronidase-fihj for adult patients with relapsed or refractory multiple myeloma who have received at least 1 prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent. In addition, this approval converts teclistamab’s 2022 accelerated approval to full traditional approval as monotherapy for adults with relapsed or refractory multiple myeloma who have received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.
This application was reviewed under the FDA Commissioner’s National Priority Review Voucher pilot program.
The approval was based on data from the Majes-TEC-3 trial (NCT05083169), a randomized, open-label, multicenter study involving 587 patients. Participants were randomized to either the teclistamab-daratumumab hyaluronidase-fihj combination group (n=291) or the investigator’s choice control group (n=296), which included standard regimens such as daratumumab hyaluronidase-fihj with pomalidomide and dexamethasone or daratumumab hyaluronidase-fihj with bortezomib and dexamethasone.
The primary end point was progression-free survival (PFS), assessed by independent review using International Myeloma Working Group 2016 criteria. Secondary end points included overall survival (OS). Median PFS in the teclistamab-daratumumab arm was not reached (NR) (95% CI, NR-NR), compared with 18.1 months (95% CI, 14.6-22.8) in the control arm (hazard ratio [HR], 0.17; 95% CI, 0.12-0.23; P<.0001). Median OS was NR in the teclistamab combination group and NR (95% CI, 41.4-NR) in the control group (HR, 0.46; 95% CI, 0.32-0.65; P<.0001).
The prescribing information includes a boxed warning for life-threatening or fatal cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome. Tecvayli is available only through a Risk Evaluation and Mitigation Strategy (REMS) program, known as Tecvayli-Talvey REMS. Other commonly reported side effects in the combination group include hypogammaglobulinemia, upper respiratory tract infections, cough, diarrhea, musculoskeletal pain, pneumonia, injection site reactions, fatigue, fever, nausea, and weight loss.
Detailed dosing instructions for teclistamab and daratumumab hyaluronidase-fihj are outlined in the prescribing information.
This approval offers an effective additional treatment option for patients with relapsed or refractory multiple myeloma based on a substantial reduction in the risk of disease progression and death observed in clinical trials.
Source
- FDA approves teclistamab in combination with daratumumab hyaluronidase-fihj for relapsed or refractory multiple myeloma. www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-teclistamab-combination-daratumumab-hyaluronidase-fihj-relapsed-or-refractory-multiple