On March 5, 2026, the U.S. Food and Drug Administration (FDA) approved teclistamab (Tecvayli) in combination with daratumumab hyaluronidase-fihj for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent.
In addition, the approval converts the 2022 accelerated approval for teclistamab as monotherapy to a traditional approval. The monotherapy indication is 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.
This approval was considered through the FDA Commissioner’s National Priority Review Voucher pilot program for accelerating the review of products with the potential to address key national priorities.
Efficacy and Safety
Efficacy for the teclistamab combination was evaluated in MajesTEC-3 (ClinicalTrials.gov identifier NCT05083169), a randomized, open-label, multi-center trial. A total of 587 patients were randomly assigned in the trial to the teclistamab and daratumumab hyaluronidase group (n = 291) or to the investigator’s choice control group of either daratumumab hyaluronidase, pomalidomide, and dexamethasone (DPd) or daratumumab hyaluronidase, bortezomib, and dexamethasone (DVd) (n = 296).
The major efficacy outcome measure was progression-free survival by independent review committee assessment based on International Myeloma Working Group 2016 criteria. Overall survival was an additional efficacy outcome measure. Median progression-free survival was not reached in the teclistamab and daratumumab hyaluronidase arm and was 18.1 months (95% confidence interval [CI] = 14.6–22.8) in the control arm (hazard ratio [HR] = 0.17, 95% CI = 0.12–0.23; P < .0001). Median overall survival was not reached in either arm (HR = 0.46, 95% CI = 0.32–0.65; P < .0001).
Prescribing information for teclistamab includes a Boxed Warning for life threatening or fatal cytokine-release syndrome and neurologic toxicity, including immune effector cell–associated neurotoxicity. Teclistamab is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), called the Tecvayli-Talvey REMS.
In addition to cytokine-release syndrome, the most common adverse effects of teclistamab in combination with daratumumab hyaluronidase include hypogammaglobulinemia, upper respiratory tract infection, cough, diarrhea, musculoskeletal pain, COVID-19, pneumonia, injection site reaction, fatigue, pyrexia, headache, nausea, gastroenteritis, and decreased weight.
Expedited Programs
This review was conducted under Project Orbis, a framework for concurrent submission and review of oncology drugs among international partners. For this review, the FDA collaborated with Health Canada (HC) and Switzerland’s Swissmedic (SMC). The applications may still be under review at the other regulatory agencies.
Additionally, the review used the Real-Time Oncology Review pilot program, which streamlines data submission prior to filing the entire clinical application, as well as the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
The application was also granted a Priority Review designation, and teclistamab has previously received Breakthrough and Orphan Drug designations.
