FDA Approves Teclistamab for Relapsed/Refractory Myeloma

By: JNCCN 360 Staff
Posted: Thursday, March 19, 2026

On March 5, the U.S. Food and Drug Administration (FDA) approved teclistamab (Tecvayli) in combination with daratumumab hyaluronidase-fihj for 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. 

Teclistamab is T-cell–redirecting bispecific antibody that targets both CD3 expressed on the surface of T cells and B-cell maturation antigen expressed on the surface of myeloma cells. Daratumumab hylaluronidase-fihj is a subcutaneous injection which allowes for faster absorption of the CD38-targeted antibody daratumumab.

The approval also converts the accelerated approval to traditional approval for teclistamab, as monotherapy, in adults 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 received accelerated approval for this indication in 2022. 

This application is part of the FDA Commissioner’s National Priority Review Voucher pilot program, which is designed to accelerate the review of products with the potential to address key national priorities.

MasjesTEC-3

Efficacy was evaluated in MajesTEC-3 (ClinicalTrials.gov identifier NCT05083169), a randomized, open-label, multicenter trial. A total of 587 patients were randomly assigned 1:1 in the trial to either the teclistamab and daratumumab hyaluronidase-fihj group (n = 291) or to the investigator’s choice control group of either daratumumab hyaluronidase-fihj, pomalidomide, and dexamethasone (DPd) or daratumumab hyaluronidase-fihj, bortezomib, and dexamethasone (DVd) (n = 296).

The major efficacy outcome measure of the study 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 (95% confidence interval [CI] = not evaluable to not evaluable) in the teclistamab and daratumumab hyaluronidase-fihj arm and was 18.1 months (95% CI = 14.6–22.8 months) in the control arm (hazard ratio [HR] = 0.17, 95% CI = 0.12–0.23, P < .0001). Median overall survival was not reached (95% CI = not evaluable to not evaluable) and not reached (95% CI = 41.4 months to not evaluable) in the respective arms (HR = 0.46, 95% CI = 0.32–0.65, P < .0001).

Safety

The prescribing information for teclistamab includes a Boxed Warning for life-threatening or fatal cytokine-release syndrome (CRS) 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 CRS, the most common side effects of teclistamab in combination with daratumumab hyaluronidase-fihj include hypogammaglobulinemia, upper respiratory tract infection, cough, diarrhea, musculoskeletal pain, COVID-19 infection, pneumonia, injection site reaction, fatigue, pyrexia, headache, nausea, gastroenteritis, and decreased weight.

Expedited Programs

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence which provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, the FDA collaborated with Health Canada and Switzerland’s Swissmedic. The applications may still be under review at the other regulatory agencies.

This review used the Real-Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

This application was granted Priority Review. Teclistamab received Breakthrough Therapy designation and Orphan Drug designation. 

FDA.gov

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