The FDA has approved teclistamab (Tecvayli, Janssen Biotech, Inc.) in combination with daratumumab and hyaluronidase-fihj (Darzalex Faspro, Janssen Biotech, Inc.) for the treatment of certain adult patients with relapsed or refractory (RR) multiple myeloma (MM).

Specifically, the combination is approved for patients with MM who have received at least one prior line of therapy including a proteasome inhibitor and an immunomodulatory agent, according to the FDA approval notice.

The FDA also converted the accelerated approval of teclistamab to traditional approval. Accelerated approval for the bispecific B-cell maturation antigen-directed CD3 T-cell engager as monotherapy for adults with RRMM and at least four prior lines of therapy was granted in 2022.

Approval for the new combination, which followed priority review, was based on findings from the randomized, open-label MajesTEC-3 trial showing significantly improved survival outcomes vs the investigator’s choice of daratumumab and hyaluronidase-fihj plus pomalidomide and dexamethasone or daratumumab and hyaluronidase-fihj plus bortezomib and dexamethasone.

Findings from the trial were presented at the American Society of Hematology (ASH) 2025 Annual Meeting and were published simultaneously in The New England Journal of Medicine.

Median progression-free survival, the primary outcome measure, was not reached in the 291 patients in the treatment arm vs 18.1 months in 296 patients in the control arm (hazard ratio [HR], 0.17). The median overall survival was not reached in either arm (HR, 0.46).

At the time of the presentation at ASH 2025, lead investigator María-Victoria Mateos, MD, PhD, said the treatment combination “generated the greatest progression-free survival treatment effect to date [in RRMM] with a plateau phase after 6 months of therapy, suggesting potential for functional cure,” as reported by Medscape Medical News.

“We consider that this synergistic immunotherapy combination is a new potential standard of care for relapsed or refractory multiple myeloma after at least one prior line of therapy, with broad potential across academic and community settings,” added Mateos, consultant physician, associate professor, and director of the Multiple Myeloma Program at the University of Salamanca, Salamanca, Spain.

Full prescribing information for teclistamab, which will be posted on Drugs@FDA, includes a boxed warning for life-threatening or fatal cytokine release syndrome and neurologic toxicity, including immune effector cell-associated neurotoxicity, the FDA said. The agent is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Tecvayli-Talvey REMS.

Cytokine release syndrome is also one of the most common side effects of teclistamab in combination with daratumumab and hyaluronidase-fihj. Others included hypogammaglobulinemia, upper respiratory tract infection, cough, diarrhea, musculoskeletal pain, COVID, pneumonia, injection site reaction, fatigue, pyrexia, headache, nausea, gastroenteritis, and decreased weight.

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape, MDedge, and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and healthcare topics. She can be reached at sworcester@mdedge.com or on X: @SW_MedReporter.